Motor representation in patients rapidly recovering after stroke: a functional magnetic resonance imaging and transcranial magnetic stimulation study

OBJECTIVE: Neuroimaging studies have suggested an evolution of the brain activation pattern in the course of motor recovery after stroke. Initially poor motor performance is correlated with an recruitment of the uninjured hemisphere that continuously vanished until a nearly normal (contralateral) activation pattern is achieved and motor performance is good. Here we were interested in the early brain activation pattern in patients who showed a good and rapid recovery after stroke. METHODS: Ten patients with first-ever ischemic stroke affecting motor areas had to perform self-paced simple or more complex movements with the affected or the unaffected hand during functional magnetic resonance imaging (fMRI). The location and number of activated voxels above threshold were determined. To study possible changes in the cortical motor output map the amplitude of the motor evoked potentials (MEP) and the extent of the excitable area were determined using transcranial magnetic stimulation (TMS). RESULTS: The pattern of activation observed with movements of the affected and the unaffected hand was similar. In the simple motor task significant (P<0.05) increases were found in the primary motor cortex ipsilateral to the movement, the supplementary motor area and the cerebellar hemisphere contralateral to the movement during performance with the affected hand compared to movements with the unaffected hand. When comparing simple with more complex movements performed with either the affected or the unaffected hand, a further tendency to increased activation in motor areas was observed. The amplitude of MEPs obtained from the affected hemisphere was smaller and the extent of cortical output maps was decreased compared to the unaffected hemisphere; but none of the patients showed MEPs at the affected hand when the ipsilateral unaffected motor cortex was stimulated. CONCLUSIONS: Despite a rapid and nearly complete motor recovery the brain activation pattern was associated with increased activity in (bilateral) motor areas as revealed with fMRI. TMS revealed impaired motor output properties, but failed to demonstrate ipsilateral motor pathways. Successful recovery in our patients may therefore rely on the increased bilateral activation of existing motor networks spared by the injury.     

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     

磁刺激运动诱发肌电位对运动机能评价的临床应用

目的：观察磁刺激运动诱发肌电位对运动机能的评价。方法：用磁刺激装置对正常人１２例，运动障碍患者３１例进行了经颅脑刺激，记录运动诱发肌电位。结果：受检测的４３例，无一例引起头痛和感觉异常，也无癫痫及意识障碍等副作用。正常人中，诱发肌电位的潜伏期相对恒定，振幅在个体间虽存有差异，但同一例左右侧几乎相同。对２０例单侧肢体功能障碍的肌力按体征分级，比较患侧和健侧的诱发肌电位，发现患侧振幅较健侧明显减低。对肌力０～２级的病例，不能诱发出肌电位。结论：磁刺激运动诱发肌电位，在临床上可在数量上正确评价肢体的运动机能，并且经颅磁刺激法是安全的。     

低频重复经颅磁刺激联合以任务为导向作业疗法对脑卒中患者上肢运动功能的康复作用

目的探讨低频重复经颅磁刺激联合以任务为导向作业疗法对脑卒中患者上肢运动功能的康复作用。方法共42例脑卒中后偏瘫患者随机接受常规康复训练和以任务为导向作业疗法(对照组,20例)以及在此基础上联合健侧运动皮质低频(1 Hz)重复经颅磁刺激(治疗组,22例),分别于治疗前、治疗4周时和治疗后3个月采用Fugl-Meyer上肢评价量表(FMA-UE)和Wolf运动功能测验(WMFT)评价上肢运动功能,记录并分析健侧运动皮质运动诱发电位潜伏期和中枢运动传导时间。结果与对照组相比,治疗组FMA-UE评分(P=0.006)和WMFT评分(P=0.024)均增加;两组不同时间点FMA-UE评分(P=0.000)和WMFT评分(P=0.000)差异有统计学意义,其中治疗4周时和治疗后3个月FMA-UE评分(均P=0.000)和WMFT评分(均P=0.000)均高于治疗前,治疗后3个月FMA-UE评分(均P=0.000)和WMFT评分(均P=0.000)亦高于治疗4周时。两组患者治疗前后健侧运动皮质运动诱发电位潜伏期(P=0.979)和中枢运动传导时间(P=0.807)差异无统计学意义,不同时间点(治疗前、治疗4周时和治疗后3个月)健侧运动皮质运动诱发电位潜伏期(P=0.085)和中枢运动传导时间(P=0.507)差异亦无统计学意义。结论脑卒中患者健侧运动皮质低频重复经颅磁刺激联合以任务为导向作业疗法可以有效改善脑卒中患者上肢运动功能,值得临床推广应用。     

The role of the intact hemisphere in recovery of midline muscles after recent monohemispheric stroke

Transcranial magnetic stimulation (TMS) of the motor cortex was used to study basic mechanisms of motor reorganization after major hemispheric stroke in humans. We sought to clarify the possible role of the intact hemisphere in motor recovery of the lingual muscles, and to evaluate the compensatory use of preexisting uncrossed motor pathways projecting to these midline muscles. TMS and bilateral surface recordings from the lingual muscles were carried out in six selected stroke patients who presented with a unilateral lingual paralysis after a limited monohemispheric ischemia. The first examination was performed during the symptomatic stage (t ₁) and was repeated after complete recovery of lingual function had been established (t ₂). The cortical motor output patterns were analyzed and compared with the data from 40 healthy controls. In the controls TMS of either hemisphere invariably produced contralateral and ipsilateral compound muscle action potentials (CMAPs), elicited through crossed and uncrossed central motor pathways, respectively. In most individuals an asymmetric cortical motor output pattern was found, as significantly greater mean CMAPs of shorter onset latencies were recorded from the contralateral lingual muscles than from the ipsilateral responses. In the six patients with a unilateral lingual paralysis a similar pattern was found on initial examination by stimulating the intact hemisphere, whereas TMS of the affected hemisphere failed to elicit any CMAP bilaterally. At t ₂ all patients had regained normal lingual function. Only one patient showed evidence of a complete recovery of the primarily affected hemisphere, as TMS now elicited normal CMAPs bilaterally. In the remaining five patients the unilateral interruption of the corticonuclear pathways persisted in spite of complete functional recovery. In these subjects the recovery of symmetric lingual movements must be attributed to the intact hemisphere. From this it is concluded that recovery of a unilateral lingual paralysis after restricted monohemispheric lesions is possible without recovery of the cortical motor projections from the affected hemisphere. In these cases the intact hemisphere is responsible for restoration of normal lingual movements, most likely by potentiating the effect of preexisting uncrossed motor pathways. Received: 26 March 1998 Accepted: 24 June 1998     

Pinging the brain with transcranial magnetic stimulation reveals cortical reactivity in time and space

BackgroundSingle-pulse transcranial magnetic stimulation (TMS) elicits an evoked electroencephalography (EEG) potential (TMS-evoked potential, TEP), which is interpreted as direct evidence of cortical reactivity to TMS. Thus, combining TMS with EEG can be used to investigate the mechanism underlying brain network engagement in TMS treatment paradigms. However, controversy remains regarding whether TEP is a genuine marker of TMS-induced cortical reactivity or if it is confounded by responses to peripheral somatosensory and auditory inputs. Resolving this controversy is of great significance for the field and will validate TMS as a tool to probe networks of interest in cognitive and clinical neuroscience.ObjectiveHere, we delineated the cortical origin of TEP by spatially and temporally localizing successive TEP components, and modulating them with transcranial direct current stimulation (tDCS) to investigate cortical reactivity elicited by single-pulse TMS and its causal relationship with cortical excitability.MethodsWe recruited 18 healthy participants in a double-blind, cross-over, sham-controlled design. We collected motor-evoked potentials (MEPs) and TEPs elicited by suprathreshold single-pulse TMS targeting the left primary motor cortex (M1). To causally test cortical and corticospinal excitability, we applied tDCS to the left M1.ResultsWe found that the earliest TEP component (P25) was localized to the left M1. The following TEP components (N45 and P60) were largely localized to the primary somatosensory cortex, which may reflect afferent input by hand-muscle twitches. The later TEP components (N100, P180, and N280) were largely localized to the auditory cortex. As hypothesized, tDCS selectively modulated cortical and corticospinal excitability by modulating the pre-stimulus mu-rhythm oscillatory power.ConclusionTogether, our findings provide causal evidence that the early TEP components reflect cortical reactivity to TMS.     

脑血管病患者经颅磁刺激运动诱发电位的研究

采用经颅磁刺激运动诱发电位（ＭＥＰ）对７２例脑血管病（ＣＶＤ）患者和５０例正常人进行检测。结果：ＣＶＤ患者瘫痪侧上肢磁刺激无反应或皮层潜伏期和中枢传导时间（ＣＭＣＴ）较正常对照组和健侧显著延长（Ｐ＜０．００１）；瘫痪侧下肢磁刺激无反应或ＣＭＣＴ较正常对照组和健侧显著延长（Ｐ＜０．０５）。脑出血与脑梗塞患者ＭＥＰ异常率无显著差异（Ｐ＞０．０５），而与临床病情轻重和病变部位密切相关。提示ＭＥＰ能客观反映ＣＶＤ患者中枢运动传导通路功能受损的情况。     

Concurrent excitation of the opposite motor cortex during transcranial magnetic stimulation to activate the abdominal muscles

The study investigated the potential for stimulation of both motor cortices during transcranial magnetic stimulation (TMS) to evoke abdominal muscle responses. Electromyographic activity (EMG) of transversus abdominis (TrA) was recorded bilaterally in eleven healthy volunteers using fine-wire electrodes. TMS at 120% motor threshold (MT) was delivered at rest and during 10% activation at 1 cm intervals from the midline to 5 cm lateral, along a line 2 cm anterior to the vertex. The optimal site to evoke responses in TrA is located 2 cm lateral to the vertex. When bilateral abdominal responses were evoked at or lateral to this site, onset of ipsilateral motor evoked potentials (MEPs) were 3–4 ms longer than contralateral MEPs. The difference between latencies is consistent with activation of faster crossed-, and slower uncrossed-corticospinal pathways from one hemisphere. However, latencies of MEPs were similar between sides when stimulation was applied more medially and were consistent with concurrent activation of crossed corticospinal tracts on both sides. The findings suggest that stimulation of both motor cortices is possible when TMS is delivered less than 2 cm from midline. Concurrent stimulation of both motor cortices can be minimised if TMS is delivered at least 2 cm lateral to midline.     

Motor responses evoked by transcranial magnetic stimulation and peripheral nerve stimulation in the ulnar innervation in amyotrophic lateral sclerosis: the effect of upper and lower motor neuron lesion

We studied the upper (UMN) and lower motor neuron (LMN) innervations of 159 hands from 81 patients with amyotrophic lateral sclerosis (ALS). Eleven patients with various chronic LMN disorders causing weakness in the abductor digiti minimi (ADM) muscle served as LMN controls. Thirty healthy subjects served as normal controls. Cortical motor threshold, central conduction time (CMCT), and motor-evoked response amplitude (MEP) after transcranial magnetic stimulation (TMS) were studied, and the MEP/M wave ratio was calculated. The data was analyzed in the ALS subjects in groups defined by ADM muscle strength and by the presence or absence of clinical signs of UMN involvement.

CMCT was not increased in the ALS or LMN disease groups. The threshold was higher in limbs with both weak ADM muscles and UMN signs. The MEP/M wave amplitude ratio was increased in weak muscles in the ALS patients, notably in limbs with no UMN signs, and also in weak muscles in patients with other chronic LMN disorders. It was frequently decreased in strong muscles. There was no difference between bulbar-onset and limb-onset ALS groups, and there was no correlation between threshold and disease duration. We suggest that expressing the data as an index and utilising the MEP/M wave amplitude ratio as a variable is a sensitive method for detecting UMN abnormality in ALS in particular in early affected muscles.     

The relationship between motor cortex excitability and severity of Alzheimer's disease: a transcranial magnetic stimulation study

Introduction

In Alzheimer's disease (AD), transcranial magnetic stimulation (TMS) studies have been limited to test motor cortical excitability. The aim of this study was to investigate the inhibitory circuits of the motor cortex and to relate these to measures of cognitive function in AD patients. Results were compared with those of a control group of healthy subjects matched for age, sex and education.

Patients and methods

Forty-five AD patients and 37 healthy volunteers were included in the study. Each participant received a neurological evaluation, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR). Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), motor evoked potential (MEP), cortical silent period (CSP), and transcallosal inhibition (TI).

Results

AD patients showed significantly reduced rMT, aMT and shorter MEP onset latency; in addition there was a prolongation of both CSP and TI. There was a significant positive correlation between the MMSE and CDR, on the one hand, and aMT and rMT, on the other hand, whereas the correlation was negative with CSP and TI durations.

Conclusion

AD is associated with hyperexcitability of the motor cortex, which supports the hypothesis that changes in GABAb and glutamate function are important factors in cognitive impairment.     

Publication trends in transcranial magnetic stimulation: a 30-year panorama

Background

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has broad diagnostic and therapeutic potential across a range of neurological and psychiatric diseases.

Automated-parameterization of the motor evoked potential and cortical silent period induced by transcranial magnetic stimulation

ObjectiveTo standardize the characterization of motor evoked potential (MEP) and cortical silent period (CSP) recordings elicited with transcranial magnetic stimulation (TMS).MethodsA computer-based, automated-parameterization program (APP) was developed and tested which provides a comprehensive set of electromyography (EMG) magnitude and temporal measures. The APP was tested using MEP, CSP, and isolated CSP (iCSP) TMS stimulus–response data from a healthy adult population (N = 13).ResultsThe APP had the highest internal reliability (Cronbach’s alpha = .98) for CSP offset time compared with two prominent automated methods. The immediate post-CSP EMG recovery level was 49% higher than the pre-TMS EMG level. MEP size (peak amplitude, mean amplitude, peak-to-peak amplitude, and area) correlated higher with effective E-field (E_eff) than other intensity measures (r ≈ 0.5 vs. r ≈ 0.3) suggesting that E_eff is better suited for standardizing MEP stimulus–response relationships.ConclusionsThe APP successfully characterized individual and mean epochs containing MEP, CSP, and iCSP responses. The APP provided common signal and temporal measures consistent with previous studies and novel additional parameters.SignificanceWith the use of the APP modeling method and the E_eff, a standard approach for the analysis and reporting of MEP–CSP complex and iCSP measurements is achievable.     

Effects of deep brain stimulation on the primary motor cortex: Insights from transcranial magnetic stimulation studies

Deep brain stimulation (DBS) implanted in different basal ganglia nuclei regulates the dysfunctional neuronal circuits and improves symptoms in movement disorders. However, the understanding of the neurophysiological mechanism of DBS is at an early stage. Transcranial magnetic stimulation (TMS) can be used safely in movement disorder patients with DBS, and can shed light on how DBS works. DBS at a therapeutic setting normalizes the abnormal motor cortical excitability measured with motor evoked potentials (MEP) produced by primary motor cortical TMS. Abnormal intracortical circuits in the motor cortex tested with paired-pulse TMS paradigm also show normalization with DBS. These changes are accompanied with improvements in symptoms after chronic DBS. Single-pulse DBS produces cortical evoked potentials recorded by electroencephalography at specific latencies and modulates motor cortical excitability at certain time intervals measured with MEP. Combination of basal ganglia DBS with motor cortical TMS at stimulus intervals consistent with the latency of cortical evoked potentials delivered in a repetitive mode produces plastic changes in the primary motor cortex. TMS can be used to examine the effects of open and closed loop DBS. Patterned DBS and TMS delivered in a repetitive mode may be developed as a new therapeutic method for movement disorder patients.     

功能性电刺激结合重复经颅磁刺激用于缺血性脑卒中偏瘫患者步行障碍恢复的临床观察

目的 观察功能性电刺激结合重复经颅磁刺激用于缺血性脑卒中偏瘫患者步行障碍恢复的临床疗效。方法 将53例缺血性脑卒中偏瘫患者随机分为对照组、治疗组、假治疗组3组,在均接受常规康复训练的基础上对照组接受功能性电刺激治疗,治疗组接受功能性电刺激及重复经颅磁刺激治疗,假治疗组接受功能性电刺激及假重复经颅磁刺激治疗; 治疗前及治疗8周后采用步态运动学参数、时间参数、距离参数及Amer-Lindholm分级对3组患者的下肢综合运动功能进行评定。结果 治疗前3组患者步态运动学参数、时间参数、距离参数及Amer-Lindholm分级评分均无显著差异(P>0.05),治疗8周后3组患者上述指标明显改善且治疗组改善幅度明显优于其余2组(P<0.05)。结论 功能性电刺激联合重复经颅磁刺激治疗有利于改善缺血性脑卒中偏瘫患者的步行运动功能。     

Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.     

Long-term changes in motor cortical organisation after recovery from subcortical stroke

The present study has investigated the long-term changes in the organisation of the corticomotor projection to the hand in a group of subjects who had sustained a subcortical hemispheric stroke up to 15 years previously and had subsequently recovered normal or near-normal motor function. Transcranial magnetic cortical stimulation (TMCS) was employed to map the topography of the primary corticomotor projection to the hand and to obtain measures of cortical motor threshold, long-latency intracortical inhibition and corticospinal conduction. Changes in motor threshold and in motor-evoked potential (MEP) amplitude and latency in keeping with persisting impairment of conduction in the corticospinal pathway were still present in the majority of subjects, whereas the duration of the post-MEP silent period, reflecting the strength of long-latency intracortical inhibition, was usually normal. Topographic shifts in the corticomotor representation relative to the unaffected side were found in the majority of subjects. In some the shifts were in the mediolateral axis suggesting reorganisation within the primary motor cortex, while in the others anteroposterior shifts were present in keeping with recruitment of premotor or postcentral cortex. The present findings indicate that changes in the physiological properties of the corticomotor projection to the hand are frequently present in subjects who have recovered motor function after a subcortical stroke and may persist indefinitely. We postulate that these changes are the result of reorganisation at cortical level and that cortical reorganisation is one of the processes which contribute to motor recovery after a subcortical lesion and which may compensate for persisting impairment of conduction in the corticospinal pathway.     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.