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.     

Development of cortical motor circuits between childhood and adulthood: A navigated TMS‐HdEEG study

Motor functions improve during childhood and adolescence, but little is still known about the development of cortical motor circuits during early life. To elucidate the neurophysiological hallmarks of motor cortex development, we investigated the differences in motor cortical excitability and connectivity between healthy children, adolescents, and adults by means of navigated suprathreshold motor cortex transcranial magnetic stimulation (TMS) combined with high‐density electroencephalography (EEG). We demonstrated that with development, the excitability of the motor system increases, the TMS‐evoked EEG waveform increases in complexity, the magnitude of induced activation decreases, and signal spreading increases. Furthermore, the phase of the oscillatory response to TMS becomes less consistent with age. These changes parallel an improvement in manual dexterity and may reflect developmental changes in functional connectivity. Hum Brain Mapp 38:2599–2615, 2017. © 2017 Wiley Periodicals, Inc.     

Direct comparison of cortical excitability to transcranial magnetic stimulation in obstructive sleep apnea syndrome and restless legs syndrome

ObjectiveChanges to transcranial magnetic stimulation (TMS) have been reported in obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS), although no direct comparison study is available. The aim of this new investigation is to assess and compare cortical excitability of OSAS and RLS patients using the same methodology and under the same experimental conditions.MethodsFourteen patients with OSAS and 12 with RLS were compared to 14 age-matched controls. All patients were untreated and had a severe degree of disease. Resting motor threshold (rMT), cortical silent period (CSP) and motor evoked potentials MEPs, as well as intracortical inhibition (ICI) and facilitation at interstimulus interval (ISI) of 3 and 10 ms, respectively, were explored from the right first dorsal interosseous muscle, during wakefulness.ResultsrMT was higher in OSAS than in RLS and controls. CSP was shorter in RLS only when compared to apneic patients, whereas it was similar between OSAS and controls. OSAS subjects exhibited slightly prolonged central motor conductivity, whereas MEP amplitude was smaller in both patient groups. The ICI ratio at ISI of 3 ms was decreased in RLS patients only.ConclusionsDistinct changes of responses at TMS were found, probably connected with the different neurophysiological substrates underlying OSAS and RLS and could not be interpreted as a mere reflection of the effects of sleep architecture alteration. TMS can be considered an additional tool for the understanding of clinical and pathophysiological aspects of sleep disorders, and possibly for the evaluation of the effect of therapy.     

Central mechanisms during fatiguing muscle exercise in muscular dystrophy and fibromyalgia syndrome: a study with transcranial magnetic stimulation

Introduction: The aim of this study was to apply paired‐pulse transcranial magnetic stimulation (TMS) to assess intracortical inhibition (ICI) during fatiguing muscle exercise in healthy humans and patients with muscular dystrophy (MD) and fibromyalgia syndrome (FMS) to obtain insight into differential central mechanisms. Methods: We studied 23 patients with MD, 16 patients with FMS, and 23 healthy controls. All participants performed a fatiguing motor task. TMS recordings were taken pre‐exercise, immediately post‐exercise, and 40 minutes post‐exercise. Results: ICI was already reduced pre‐exercise in MD and FMS, whereas ICI decreased significantly during fatiguing muscle exercise only in healthy subjects. Discussion: Reduced baseline ICI in patients might prevent further utilization of this presumably compensatory mechanism during fatiguing muscle exercise. Although reduced baseline to be ICI in MD can be explained as compensatory due to peripheral weakness, in FMS reduced ICI must be considered an indicator of primary central disinhibition. Muscle Nerve, 2011     

Motor cortex dysfunction revealed by cortical excitability studies in Parkinson's disease: influence of antiparkinsonian treatment and cortical stimulation.

Single or paired pulse paradigms of transcranial magnetic stimulation (TMS) provide several parameters to test motor cortex excitability, such as motor threshold (MT), motor evoked potential (MEP) amplitude, electromyographic silent period to cortical stimulation (CSP) and intracortical facilitation (ICF) or inhibition (ICI). Various changes in TMS parameters, revealing motor cortex dysfunction, were found in patients with Parkinson's disease (PD). For instance, low MT and increased MEP size disclosed an enhanced corticospinal motor output at rest, while reduced ICF and failure of MEP size increase during contraction suggested defective facilitatory cortical inputs, particularly for movement execution. Inhibitory cortical pathways were also found less excitable at rest (reduced ICI) and sometimes during contraction (shortened CSP). By restoring cortical inhibition, dopaminergic drugs and deep brain stimulation probably overcome the difficulty to focus neuronal activity onto the appropriate network required for a specific motor task. The application of repetitive TMS trains over motor cortical areas also showed some effect on cortical excitability, opening perspectives to consider the motor cortex as a target for therapeutic neuromodulation in PD. However, systematic studies of cortical excitability remained to be performed in large series of patients with PD, taking into account disease stage, clinical symptoms and medication influence.     

Altered cortical excitability in obsessive-compulsive disorder

OBJECTIVE: To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD). BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders. METHODS: We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus. RESULTS: Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics. CONCLUSIONS: The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.     

Triad-conditioning Transcranial Magnetic Stimulation in Parkinson's Disease

BackgroundTranscranial magnetic stimulation (TMS) has been used to reveal excitability changes of the primary motor cortex (M1) in Parkinson's disease (PD). Abnormal rhythmic neural activities are considered to play pathophysiological roles in the motor symptoms of PD. The cortical responses to external rhythmic stimulation have not been studied in PD. We recently reported a new method of triad-conditioning TMS to detect the excitability changes after rhythmic conditioning stimuli, which induce facilitation by 40-Hz stimulation in healthy volunteers.ObjectiveWe applied a triad-conditioning TMS to PD patients to reveal the motor cortical response characteristics to rhythmic TMS.MethodsThe subjects included 13 PD patients and 14 healthy volunteers. Three conditioning stimuli over M1 at an intensity of 110% active motor threshold preceded the test TMS at various inter-stimulus intervals corresponding to 10–200 Hz.ResultsThe triad-conditioning TMS at 40 Hz induced no MEP enhancement in PD patients in either the On or Off state, in contrast to the facilitation observed in the normal subjects. Triad-conditioning TMS at 20–33 Hz in the beta frequency elicited significant MEP suppression in PD patients. The amount of suppression at 20 Hz positively correlated with the UPDRS III score.ConclusionWe observed abnormal M1 responses to rhythmic TMS in PD. The suppression induced by beta frequency stimulation and no facilitation by 40-Hz stimulation may be related to abnormal beta and gamma band activities within the cortical-basal ganglia network in PD patients. The motor cortical response to rhythmic TMS may be an additional method to detect physiological changes 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.     

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation

ObjectiveTo investigate changes in cortical excitability and short-term synaptic plasticity we delivered 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in 11 patients with mild-to-moderate Alzheimer’s disease (AD) before and after chronic therapy with rivastigmine.MethodsResting motor threshold (RMT), motor evoked potential (MEP), cortical silent period (CSP) after single stimulus and MEP facilitation during rTMS trains were tested three times during treatment. All patients underwent neuropsychological tests before and after receiving rivastigmine. rTMS data in patients were compared with those from age-matched healthy controls.ResultsAt baseline, RMT was significantly lower in patients than in controls whereas CSP duration and single MEP amplitude were similar in both groups. In patients, rTMS failed to induce the normal MEP facilitation during the trains. Chronic rivastigmine intake significantly increased MEP amplitude after a single stimulus, whereas it left the other neurophysiological variables studied unchanged. No significant correlation was found between patients’ neuropsychological test scores and TMS measures.ConclusionsChronic treatment with rivastigmine has no influence on altered cortical excitability and short-term synaptic plasticity as tested by 5 Hz-rTMS.SignificanceThe limited clinical benefits related to cholinesterase inhibitor therapy in patients with AD depend on factors other than improved plasticity within the cortical glutamatergic circuits.     

Associative plasticity in intracortical inhibitory circuits in human motor cortex

ObjectivePaired associative stimulation (PAS) is a transcranial magnetic stimulation technique inducing Hebbian-like synaptic plasticity in the human motor cortex (M1). PAS is produced by repetitive pairing of a peripheral nerve shock and a transcranial magnetic stimulus (TMS). Its effect is assessed by a change in size of a motor evoked response (MEP). MEP size results from excitatory and inhibitory influences exerted on cortical pyramidal cells, but no robust effects on inhibitory networks have been demonstrated so far.MethodIn 38 healthy volunteers, we assessed whether a PAS intervention influences three intracortical inhibitory circuits: short (SICI) and long (LICI) intracortical inhibitions reflecting activity of GABA_A and GABA_B interneurons, respectively, and long afferent inhibition (LAI) reflecting activity of somatosensory inputs.ResultsAfter PAS, MEP sizes, LICI and LAI levels were significantly changed while changes of SICI were inconsistent. The changes in LICI and LAI lasted 45 min after PAS. Their direction depended on the delay between the arrival time of the afferent volley at the cortex and the TMS-induced cortical activation during the PAS.ConclusionsPAS influences inhibitory circuits in M1.SignificancePAS paradigms can demonstrate Hebbian-like plasticity at selected inhibitory networks as well as excitatory networks.     

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.     

Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?

ObjectiveTo assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD).MethodsThe study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects.ResultsThe patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters.ConclusionsOnly subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD.SignificanceThe clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile.     

Detecting poststroke cortical motor maps with biphasic single- and monophasic paired-pulse TMS

BackgroundResidual corticospinal connections are the precondition for poststroke motor recovery and necessary for targeted interventions. In severely affected patients, standard transcranial magnetic stimulation (TMS) may lead to false negative findings.ObjectiveDetecting the cortical representation of paralyzed forearm muscles by applying different stimulation techniques and maps beyond the hotspot.MethodsIn seventeen chronic stroke patients with severe motor deficits, navigated biphasic single (SP) and monophasic paired-pulse (PP) TMS was applied at 100% stimulator output to an extended cortical area in the ipsilesional hemisphere, while recording surface EMG of the extensor carpi radialis muscle.ResultsIn eleven patients, residual connectivity to the paralyzed forearm was detected with either mapping technique (five SP and PP, four PP only, two SP only). In five patients, connections originated from non-primary motor areas.ConclusionThese results could be instrumental for identifying candidates and stimulation targets for novel neuromodulation interventions in the context of neurorehabilitation.     

Non-homogeneous effect of levodopa on inhibitory circuits in Parkinson's disease and dyskinesia

IntroductionLevodopa-induced dyskinesia in patients with Parkinson's disease (PD) has been shown to be associated with an abnormal plasticity in the motor cortex. We investigated whether changes in the excitability of inhibitory and excitatory motor circuits could underlie maladaptive mechanisms associated with dyskinesia.MethodsUsing single and paired transcranial magnetic stimulation (TMS), we studied motor threshold, silent period (SP) duration, intracortical facilitation (ICF), short intracortical inhibition (SICI) and low- and high-intensity long intracortical inhibition (LICI) in 10 dyskinetic and 10 non-dyskinetic patients, matched for disease and treatment duration, before (OFF state) and after (ON state) levodopa, and in 10 healthy controls.ResultsIn the OFF state, the two groups of patients showed similar motor cortex excitability with a reduced SICI compared to controls. LICI was weaker and increasing stimulation intensity had a lower effect on SP duration in dyskinetic patients than in controls. In dyskinetic patients, in contrast to non-dyskinetic patients, levodopa failed to increase SICI and SP duration, and potentiated to a lesser extent the effect of increasing the stimulation intensity on LICI. Although levodopa improved motor symptoms to a similar extent in both dyskinetic and non-dyskinetic patients, it failed to activate effectively the excitability of the inhibitory systems in dyskinetic patients.DiscussionThese findings suggest that dyskinesia is associated with an abnormal effect of levodopa on cortical motor inhibitory circuits.     

EEG oscillations and magnetically evoked motor potentials reflect motor system excitability in overlapping neuronal populations

ObjectiveTo understand the relationship between neuronal excitability reflected by transcranial magnetic stimulation (TMS) evoked motor potentials (MEPs) and spontaneous oscillation amplitude and phase.MethodsWe combined spontaneous EEG measurement with motor cortex TMS and recorded MEP amplitudes from abductor digiti minimi (ADM).ResultsMidrange-beta oscillations over the stimulated left motor cortex were, on average, weaker before large- than small-amplitude MEPs. The phase of occipital midrange-beta oscillations was related to the MEP amplitudes.ConclusionsThe present results support the view that MEP and Rolandic beta oscillation amplitudes are associated with motor cortical excitability. However, oscillations seen in EEG reflect the excitability of a large population of cortical neurons, and MEP amplitude is affected also by spinal excitability and action potential desynchronization. Thus, MEP and EEG oscillation amplitudes are not strongly correlated. In addition, even during rest, motor system excitability appears to be related to activity in occipital areas at frequency ranges associated with visuomotor processing.SignificanceThe ability of spontaneous oscillations and MEPs to inform us about cortical excitability is clarified. For example, it is suggested that oscillatory activity at non-motor sites might be related to motor system excitability at rest.     

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.     

Functional involvement of cerebral cortex in human narcolepsy

Abstract The pathophysiology of human narcolepsy is still poorly understood. The hypoactivity of some neurotransmitter systems has been hypothesised on the basis of the canine model. To determine whether narcolepsy is associated with changes in excitability of the cerebral cortex, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in 13 patients with narcolepsy and in 12 control subjects. We used several TMS paradigms that can provide information on the excitability of the motor cortex. Resting and active motor thresholds were higher in narcoleptic patients than in controls and intracortical inhibition was more pronounced in narcoleptic patients. No changes in the other evaluated measures were detected. These results are consistent with an impaired balance between excitatory and inhibitory intracortical circuits in narcolepsy that leads to cortical hypoexcitability. We hypothesise that the deficiency of the excitatory hypocretin/orexin-neurotransmitter-system in narcolepsy is reflected in changes of cortical excitability since circuits originating in the lateral hypothalamus and in the basal forebrain project widely to the neocortex, including motor cortex. This abnormal excitability of cortical networks could be the physiological correlate of excessive daytime sleepiness and it could be the substrate for allowing dissociated states of wakefulness and sleep to emerge suddenly while patients are awake, which constitute the symptoms of narcolepsy.     

Preferential Activation of Unique Motor Cortical Networks With Transcranial Magnetic Stimulation: A Review of the Physiological,Functional, and Clinical Evidence

ObjectivesThe corticospinal volley produced by application of transcranial magnetic stimulation (TMS) over primary motor cortex consists of a number of waves generated by trans-synaptic input from interneuronal circuits. These indirect (I)-waves mediate the sensitivity of TMS to cortical plasticity and intracortical excitability and can be assessed by altering the direction of cortical current induced by TMS. While this methodological approach has been conventionally viewed as preferentially recruiting early or late I-wave inputs from a given populations of neurons, growing evidence suggests recruitment of different neuronal populations, and this would strongly influence interpretation and application of these measures. The aim of this review is therefore to consider the physiological, functional, and clinical evidence for the independence of the neuronal circuits activated by different current directions.Materials and MethodsTo provide the relevant context, we begin with an overview of TMS methodology, focusing on the different techniques used to quantify I-waves. We then comprehensively review the literature that has used variations in coil orientation to investigate the I-wave circuits, grouping studies based on the neurophysiological, functional, and clinical relevance of their outcomes.ResultsReview of the existing literature reveals significant evidence supporting the idea that varying current direction can recruit different neuronal populations having unique functionally and clinically relevant characteristics.ConclusionsFurther research providing greater characterization of the I-wave circuits activated with different current directions is required. This will facilitate the development of interventions that are able to modulate specific intracortical circuits, which will be an important application of TMS.     

Noninvasive neurostimulation in chronic stroke: a double-blind randomized sham-controlled testing of clinical and corticomotor effects

Abstract

Background:

Repetitive peripheral magnetic stimulation (RPMS) is a painless and noninvasive method to produce afferents via the depolarization of the peripheral nervous system. A few studies tested RPMS after-effects on cerebral plasticity and motor recovery in stroke individuals, but evidences remain limited.

Objectives:

This study aimed to explore whether RPMS could mediate improvements in corticomotor and clinical outcomes associated with ankle impairments in chronic stroke.

Methods:

Eighteen subjects with chronic stroke were randomly allocated to RPMS or sham group and compared to 14 healthy subjects. Stimulation was applied over the paretic tibialis anterior (TA). Ankle impairments on the paretic side and ipsilesional TA cortical motor representation were tested clinically and by transcranial magnetic stimulation (TMS), respectively.

Results:

In the RPMS group, ankle dorsiflexion mobility and maximal isometric strength increased and resistance to plantar flexor stretch decreased. The magnitude of change seemed to be related to cortical and corticospinal integrity. Sham stimulation yielded no effect. Changes in TMS outcome and their relationships with clinical improvements were limited.

Conclusions:

RPMS improved ankle impairments in chronic stroke likely by a dynamic influence of sensory inputs on synaptic plasticity. The neurophysiological mechanisms potentially underlying the clinical effects are unclear. More studies are warranted to test the spinal and hemispheric changes responsible for the clinical improvements with emphasis on circuits spared by the lesion.     

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