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.     

Effects on motor learning of transcranial alternating current stimulation applied over the primary motor cortex and cerebellar hemisphere

Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation that modulates oscillatory neural activity in the cortical area under the electrodes. Gamma (γ)-tACS applied over the primary motor cortex (M1) and cerebellar hemisphere is known to improve motor performance; however, it is not yet known whether it affects motor learning. Thus, here we investigated whether γ-tACS applied over the M1 and cerebellar hemisphere affects motor learning. This study involved 30 healthy subjects (14 females, 16 males) performing a visuomotor control task (eight trials) during an administration of either γ-tACS or a sham stimulation (15 subjects per condition) over their right M1 and left cerebellar hemisphere. Each subject performed five trials after 24 h. The motor learning efficiency, motor learning retention and re-motor learning efficiency in each condition were compared. The motor learning retention in the γ-tACS condition was significantly higher than that in the sham condition (p = 0.031). Thus, subjects who were administered γ-tACS maintained their motor performance the next day better than sham-stimulated subjects. There was no significant difference between the conditions in the motor learning efficiency and those in the re-motor learning efficiency. Our results demonstrate that γ-tACS administered over the M1 and cerebellar hemisphere during a motor learning task can enhance motor learning retention.     

帕金森病患者运动皮质兴奋性的经颅磁刺激研究

目的:本研究拟应用低频重复性经颅磁刺激(rTMS)分别刺激帕金森病(PD)患者M1手代表区(M1Hand)及运动前区(PMC),探讨不同干预手段对运动皮质兴奋性的影响,以及M1与PMC间的联系。方法:对18名确诊PD患者先后进行4种不同干预,即口服美多芭、低频rTMS刺激M1Hand(0.5Hz,100%静息阈值,共1600次脉冲)、低频rTMS刺激PMC(0.5Hz,100%静息阈值,共1600次脉冲)以及假刺激。于每次干预前后各进行临床评价并测定运动诱发电位(MEP)相关指标。结果:①口服美多芭后UPDRSⅢ(P=0.001)以及其中有关僵直(P=0.001)、运动迟缓(P<0.001)的评分均较服药前显著改善。三种不同磁刺激干预产生结果不同,M1Hand组UPDRSⅢ减低(P=0.015),僵直(P=0.010)、运动迟缓(P=0.004)亦有所改善;PMC组UPDRSⅢ较干预前减低(P=0.046),僵直评分亦减低,但无显著性意义(P=0.163);②口服美多芭1h后MEP120减低(P=0.002),CSP延长(P=0.006);M1Hand组MEP120无著变,而CSP延长(P=0.015);PMC组MEP120减低(P=0.004),而CSP无著变;假刺激组则均无显著性改变。结论:低频rTMS对不同脑区产生的效应不同:刺激M1可使CSP延长;而刺激PMC可使MEP波幅减低。     

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.     

Novel ‘hunting’ method using transcranial magnetic stimulation over parietal cortex disrupts visuospatial sensitivity in relation to motor thresholds

There is considerable inter-study and inter-individual variation in the scalp location of parietal sites where transcranial magnetic stimulation (TMS) may modulate visuospatial behaviours (e.g. see Ryan, Bonilha, & Jackson, 2006); and no clear consensus on methods for identifying such sites. Here we introduce a novel TMS “hunting paradigm” that allows rapid, reliable identification of a site over the right anterior intraparietal sulcus (IPS), where short trains (at 10 Hz for 0.5 s) of TMS disrupt performance of a visuospatial task. The task involves detection of a small peripheral gap (at 14° eccentricity), on one or other (known) side of an extended (29°) horizontal line centred on fixation. Signal-detection analysis confirmed that TMS at the right IPS site reduced sensitivity (d′) for gap targets in the left visual hemifield. A further experiment showed that the same right-parietal TMS increased sensitivity instead for gaps in the right hemifield. Comparing TMS across a grid of scalp locations around the identified ‘hotspot’ confirmed the spatial-specificity of the effective site. Assessment of the TMS intensity required to produce the phenomena found this was linearly related to individuals’ resting motor TMS threshold over hand M1. Our approach provides a systematic new way to identify an effective site and intensity in individuals, at which TMS over right-parietal cortex reliably changes visuospatial sensitivity.     

导航经颅磁刺激定位手运动功能区初步研究

目的探讨导航经颅磁刺激定位双手运动功能区的准确性和安全性。方法采用导航经颅磁刺激对10例右利手的健康志愿者双手第一骨间背侧肌进行刺激,定位双手运动功能区及其边界,记录阳性位点坐标和运动诱发电位,并计算双手运动功能区面积。结果 10例受试者均成功定位双手运动功能区,主要定位于中央前回"Ω"区及其周围;右手运动功能区面积大于左手[(6.22±0.76)cm2对(4.30±0.40)cm~2;t=7.078,P=0.000];其中4例表现出困倦,无一例出现头痛、癫发作等不良反应。结论导航经颅磁刺激定位手运动功能区准确、安全,可作为术前定位运动功能区和研究运动功能重塑的辅助方法。     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation

Summary Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

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.

Transcranial magnetic stimulation: specific and non-specific facilitation of magnetic motor evoked potentials

Summary Different physiological mechanisms of facilitation of latencies and amplitudes of magnetic motor evoked potentials (MEPs) were evaluated in a cohort of 140 healthy volunteers. The potentials were induced at the vertex and recorded at the abductor pollicis brevis. The aim of the present investigation was to compare physiological mechanisms which presumably facilitate motor pathways at the cortical level with those known to occur during contraction of small hand muscles. When compared with MEPs at rest, the maximum average decrease of latencies (1.5, SD 1.1 ms) as well as the highest increase of peak to peak amplitudes (2.6, SD 2.1 mV) was observed during exertion of a voluntary background force, at the muscle recorded from. Pre-innervation of a neighbouring muscle (abductor digiti minimi) led to a lesser average decrease of latencies by 1.0, SD 1.1 ms and an average increase of amplitudes by only 0.5, SD 1.5 mV. Non-specific manoeuvres, like sticking out the tongue or counting aloud, reduced mean latencies slightly by 0.4 ms, SD 0.8 ms and 0.3 SD 0.85 ms respectively, but increased amplitudes markedly by an average of 1.0, SD 1.6 mV and 0.8, SD 1.4mV respectively. It is concluded that facilitation of MEPs by non-specific manoeuvres occurs and must be taken into account when evaluating MEPs.     

Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis

Noninvasive brain stimulation has been demonstrated to modulate cortical activity in humans. In particular, theta burst stimulation (TBS) has gained notable attention due to its ability to induce lasting physiological changes after short stimulation durations. The present study aimed to provide a comprehensive meta-analytic review of the efficacy of two TBS paradigms; intermittent (iTBS) and continuous (cTBS), on corticospinal excitability in healthy individuals. Literature searches yielded a total of 87 studies adhering to the inclusion criteria. iTBS yielded moderately large MEP increases lasting up to 30 min with a pooled SMD of 0.71 (p < 0.00001). cTBS produced a reduction in MEP amplitudes lasting up to 60 min, with the largest effect size seen at 5 min post stimulation (SMD = −0.9, P < 0.00001). The collected studies were of heterogeneous nature, and a series of tests conducted indicated a degree of publication bias. No significant change in SICI and ICF was observed, with exception to decrease in SICI with cTBS at the early time point (SMD = 0.42, P = 0.00036). The results also highlight several factors contributing to TBS efficacy, including the number of pulses, frequency of stimulation and BDNF polymorphisms. Further research investigating optimal TBS stimulation parameters, particularly for iTBS, is needed in order for these paradigms to be successfully translated into clinical settings.     

High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson's disease: A randomized controlled trial

BackgroundPain is common in Parkinson's disease, and there is no effective treatment. We conducted a clinical trial to determine whether high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex alleviates musculoskeletal pain in patients with Parkinson's disease.MethodsIn this single-center and double-blind trial, 52 patients with Parkinson's disease and musculoskeletal pain were randomly allocated to 26-member groups receiving 5 sessions of either 20-Hz repetitive transcranial magnetic stimulation or sham stimulation over the primary motor cortex. The participants underwent assessments in the “ON” medication state at baseline, after the fifth session, and at 2- and 4-week follow-up timepoints. The primary outcomes were pain scores on a numeric rating scale. The secondary outcomes were scores on clinical scales assessing motor symptoms, depression, anxiety, autonomic symptoms, sleep quality, and the overall severity of Parkinson's disease.ResultsAnalyses revealed significant group × time interactions for numeric rating scale pain scores (p < 0.001), motor symptom scores (p < 0.001), depression scores (p = 0.009), anxiety scores (p = 0.013), and overall disease severity scores (p < 0.001). Post hoc analyses confirmed that the repetitive transcranial magnetic stimulation group, but not the sham stimulation group, exhibited significant improvements in numeric rating scale pain scores, motor symptom scores, depression scores, anxiety scores, and overall disease severity scores.ConclusionHigh-frequency repetitive transcranial magnetic stimulation over the primary motor cortex may be an effective adjunct therapy for alleviating musculoskeletal pain in patients with Parkinson's disease.     

Reliability of the 'observation of movement' method for determining motor threshold using transcranial magnetic stimulation

The aim of this study was to establish the reliability of the observation of movement (OM) method for obtaining motor threshold (MT) in transcranial magnetic stimulation (TMS). MTs were obtained on separate days, following separate hunting procedures, for both left and right motor cortex (M1), with one or multiple estimates obtained from the same hemisphere within a single session. MTs obtained using the OM method were highly reliable and reproducible on different days (left M1: r = .98, p < .0001; right M1: r = .97, p < .0001). MTs were not influenced by the order of acquisition when two hemispheres were stimulated in the same session [F(1,22) = .12, p = .73] or by the collection of additional MTs as part of the distance-adjusted procedure [F(1,23) = .74, p = .40]. The results verify the reliability of the OM method and confirm its viability for the safe and efficient application of TMS to the left and right M1. The OM method is a reliable technique for obtaining MT and is relatively simple and quick to run. It therefore provides an effective procedure for research and clinical applications.     

Altered response to repetitive transcranial magnetic stimulation in patients with chronic primary insomnia

BackgroundWe aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls.MethodsMedian peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T₀), after the first train of a single rTMS session (T₁), and after the whole rTMS procedure (T₂). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s.ResultsResting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T₀. A reduction of MEP size was observed at both T₁ and T₂ in all subjects, but this was significantly less pronounced in patients than in control subjects.ConclusionsThe lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI.     

Determination of motor threshold using visual observation overestimates transcranial magnetic stimulation dosage: Safety implications

ObjectiveWhile the standard has been to define motor threshold (MT) using EMG to measure motor cortex response to transcranial magnetic stimulation (TMS), another method of determining MT using visual observation of muscle twitch (OM-MT) has emerged in clinical and research use. We compared these two methods for determining MT.MethodsLeft motor cortex MTs were found in 20 healthy subjects. Employing the commonly-used relative frequency procedure and beginning from a clearly suprathreshold intensity, two raters used motor evoked potentials and finger movements respectively to determine EMG-MT and OM-MT.ResultsOM-MT was 11.3% higher than EMG-MT (p < 0.001), ranging from 0% to 27.8%. In eight subjects, OM-MT was more than 10% higher than EMG-MT, with two greater than 25%.ConclusionsThese findings suggest using OM yields significantly higher MTs than EMG, and may lead to unsafe TMS in some individuals. In more than half of the subjects in the present study, use of their OM-MT for typical rTMS treatment of depression would have resulted in stimulation beyond safety limits.SignificanceFor applications that involve stimulation near established safety limits and in the presence of factors that could elevate risk such as concomitant medications, EMG–MT is advisable, given that safety guidelines for TMS parameters were based on EMG-MT.     

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.     

The involvement of primary motor cortex in mental rotation revealed by transcranial magnetic stimulation

We used single‐pulse transcranial magnetic stimulation of the left primary hand motor cortex and motor evoked potentials of the contralateral right abductor pollicis brevis to probe motor cortex excitability during a standard mental rotation task. Based on previous findings we tested the following hypotheses. (i) Is the hand motor cortex activated more strongly during mental rotation than during reading aloud or reading silently? The latter tasks have been shown to increase motor cortex excitability substantially in recent studies. (ii) Is the recruitment of the motor cortex for mental rotation specific for the judgement of rotated but not for nonrotated Shepard & Metzler figures? Surprisingly, motor cortex activation was higher during mental rotation than during verbal tasks. Moreover, we found strong motor cortex excitability during the mental rotation task but significantly weaker excitability during judgements of nonrotated figures. Hence, this study shows that the primary hand motor area is generally involved in mental rotation processes. These findings are discussed in the context of current theories of mental rotation, and a likely mechanism for the global excitability increase in the primary motor cortex during mental rotation is proposed.     

Confounding effects of caffeine on neuroplasticity induced by transcranial alternating current stimulation and paired associative stimulation

ObjectiveWe examined the effects of caffeine, time of day, and alertness fluctuation on plasticity effects after transcranial alternating current stimulation (tACS) or 25 ms paired associative stimulation (PAS25) in caffeine-naïve and caffeine-adapted subjects.MethodsIn two randomised, double-blinded, cross-over or placebo-controlled (caffeine) studies, we measured sixty subjects in eight sessions (n = 30, Male: Female = 1:1 in each study).ResultsWe found caffeine increased motor cortex excitability in caffeine naïve subjects. The aftereffects in caffeine naïve subjects were enhanced and prolonged when combined with PAS 25. Caffeine also increased alertness and the motor evoked potentials (MEPs) were reduced under light deprivation in caffeine consumers both with and without caffeine. In caffeine consumers, the time of day had no effect on tACS-induced plasticity.ConclusionsWe conclude that caffeine should be avoided or controlled as confounding factor for brain stimulation protocols. It is also important to keep the brightness constant in all sessions and study groups should not be mixed with caffeine-naïve and caffeine consuming participants.SignificanceCaffeine is one of the confounding factors in the plasticity induction studies and it induces different excitability effects in caffeine-naïve and caffeine-adapted subjects.This study was registered in the ClinicalTrials.gov with these registration IDs:1) NCT03720665 https://clinicaltrials.gov/ct2/results?cond=NCT03720665&term=&cntry=&state=&city=&dist=2) NCT04011670 https://clinicaltrials.gov/ct2/results?cond=&term=NCT04011670&cntry=&state=&city=&dist=     

Test-retest reliability of transcranial magnetic stimulation EEG evoked potentials

Background

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (TMS-EEG), offer a powerful tool for measuring causal interactions in the human brain. However, the test-retest reliability of TEPs, critical to their use in clinical biomarker and interventional studies, remains poorly understood.

Measuring latency distribution of transcallosal fibers using transcranial magnetic stimulation

BackgroundNeuroimaging technology is being developed to enable non-invasive mapping of the latency distribution of cortical projection pathways in white matter, and correlative clinical neurophysiological techniques would be valuable for mutual verification. Interhemispheric interaction through the corpus callosum can be measured with interhemispheric facilitation and inhibition using transcranial magnetic stimulation.ObjectiveTo develop a method for determining the latency distribution of the transcallosal fibers with transcranial magnetic stimulation.MethodsWe measured the precise time courses of interhemispheric facilitation and inhibition with a conditioning-test paired-pulse magnetic stimulation paradigm. The conditioning stimulus was applied to the right primary motor cortex and the test stimulus was applied to the left primary motor cortex. The interstimulus interval was set at 0.1 ms resolution. The proportions of transcallosal fibers with different conduction velocities were calculated by measuring the changes in magnitudes of interhemispheric facilitation and inhibition with interstimulus interval.ResultsBoth interhemispheric facilitation and inhibition increased with increment in interstimulus interval. The magnitude of interhemispheric facilitation was correlated with that of interhemispheric inhibition. The latency distribution of transcallosal fibers measured with interhemispheric facilitation was also correlated with that measured with interhemispheric inhibition.ConclusionsThe data can be interpreted as latency distribution of transcallosal fibers. Interhemispheric interaction measured with transcranial magnetic stimulation is a promising technique to determine the latency distribution of the transcallosal fibers. Similar techniques could be developed for other cortical pathways.