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.     

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。     

Correlation between disability and transcranial magnetic stimulation abnormalities in patients with multiple sclerosis

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating disorder of the central nervous system. Clinical evaluation, MRI, cerebrospinal fluid testing and evoked potentials (EP) are among the available methods utilized for disease diagnosis and monitoring. To date, no surrogate markers have been established to assess disease evolution and progression. The aim of this study is to assess motor evoked potentials (MEP) of MS patients by transcranial magnetic stimulation (TMS) and investigate the possible correlations between TMS abnormalities and disability in the patient group, which includes a subgroup with no apparent pyramidal tract dysfunction. A total of 131 clinically definite MS patients were included in the study. Motor responses to TMS stimulation were recorded. Absent values, decreases in amplitude, prolongation of latency and central motor conduction time (CMCT) were considered as abnormal. A total of 109 (83%) patients displayed abnormal MEP amplitude, 68 (52%) displayed MEP latency, and 64 (49%) displayed CMCT abnormalities. Abnormal CMCT, latency and amplitude results were correlated with Expanded Disability Status Scale scores (p < 0.001). Our results indicate that TMS-EP in MS patients is correlated with disability, and that these findings may support the role of EPs in predicting disability even in subclinical presentations.     

Transcranial magnetic stimulation modulation of corticospinal excitability by targeting cortical I-waves with biphasic paired-pulses

Background

Transcranial magnetic stimulation (TMS) induced I-wave behavior can be demonstrated at neuronal population level using paired-pulses and by observing short-interval cortical facilitation (SICF). Advancements in stimulator technology have made it possible to apply biphasic paired-pulses to induce SICF.

Neurophysiological evaluation of sensorimotor functions of the leg: comparison of evoked cortical potentials following electrical and mechanical stimulation,long-latency muscle responses,and transcranial magnetic stimulation

Summary Twenty-two patients with localized lesions of the central nervous system (unilateral cerebral ischaemia, cervical myelopathy, spinal tumour, familial spastic paraplegia) underwent neurophysiological evaluation of sensorimotor deficits of the leg. Functional methods using muscle stretch as stimulus, i.e. long-latency muscle responses and cortical potentials evoked by dorsiflection of the foot, were compared with transcranial magnetic stimulation and somatosensory evoked cortical potentials following electrical stimulation of the posterior tibial nerve. The functional neurophysiological methods yielded no diagnostic superiority with respect to the procedures using artificial (i.e. magnetic and electrical) stimulation. However, in most cases of missing compound motor action potentials following transcranial magnetic stimulation or missing electrically evoked cortical potentials, the long-latency muscle responses still allowed quantitative assessment of sensorimotor function.     

Motor evoked potentials to magnetic stimulation: technical considerations and normative data from 50 subjects

Summary Magnetic stimulation of the brain and cervical and lumbar spinal roots was performed on 50 healthy volunteers. Compound muscle action potentials (CMAPs) were recorded from biceps brachii, abductor digiti minimi (ADM), rectus femoris and tibiahs anterior (TA). We assessed central conduction times by subtraction of peripheral from central latencies and compared results using either spinal root stimulation or the F-wave method. Side-to-side differences of total conduction time, peripheral conduction time and central conduction time (CCT) were measured and the effect of clockwise vs counterclockwise stimulations on latencies and sizes of CMAPs is emphasized. Amplitudes and areas of CMAPs were expressed as a percentage of the peripheral M response for ADM and TA. There was a positive correlation between CCT to the lumbosacral region and height, but not between the cervical region and height. No correlation was observed between genders and central conduction times, amplitudes or areas of CMAPs.     

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non‐invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long‐lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS‐I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS‐I. TMS examinations also revealed that the nature of motor dysfunction in CRPS‐I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS‐I patients. Two studies have begun to therapeutically use rTMS. This non‐invasive brain stimulation technique could have therapeutic utility in CRPS, but further well‐designed studies are needed to corroborate initial findings.     

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.     

Transcranial magnetic stimulation in developmental stuttering: Relations with previous neurophysiological research and future perspectives

Developmental stuttering (DS) is a disruption of the rhythm of speech, and affected people may be unable to execute fluent voluntary speech. There are still questions about the exact causes of DS. Evidence suggests there are differences in the structure and functioning of motor systems used for preparing, executing, and controlling motor acts, especially when they are speech related. Much research has been obtained using neuroimaging methods, ranging from functional magnetic resonance to diffusion tensor imaging and electroencephalography/magnetoencephalography. Studies using transcranial magnetic stimulation (TMS) in DS have been uncommon until recently. This is surprising considering the relationship between the functionality of the motor system and DS, and the wide use of TMS in motor-related disturbances such as Parkinson’s Disease, Tourette’s Syndrome, and dystonia. Consequently, TMS could shed further light on motor aspects of DS. The present work aims to investigate the use of TMS for understanding DS neural mechanisms by reviewing TMS papers in the DS field. Until now, TMS has contributed to the understanding of the excitatory/inhibitory ratio of DS motor functioning, also helping to better understand and critically review evidence about stuttering mechanisms obtained from different techniques, which allowed the investigation of cortico-basal-thalamo-cortical and white matter/connection dysfunctions.     

Transcranial magnetic stimulation and Parkinson’s disease

While motor cortical areas are the main targets of the integrative activity of basal ganglia, their main output consists of the corticospinal system. Transcranial magnetic stimulation (TMS), a relatively new method to investigate corticospinal physiology, has been widely used to assess possible changes secondary to Parkinson’s disease (PD). The use of single- and paired-pulse TMS, two varieties of the original technique, disclosed multiple functional alterations of the corticospinal pathway. For instance, when the latter was tested at ‘rest’, or in response to somesthetic afferents, it showed excess excitability or reduced inhibition. In turn, during production of a voluntary output, its activation was defective, or inadequately modulated. One major mechanism may be a dysfunction of the interneurons mediating the level of excitation within cortical area 4. For instance, there is a shortening of the so-termed ‘central silent period’, which is a complex, TMS-induced, inhibitory phenomenon possibly mediated by activation of GABA_B receptors. The so-called ‘short-interval intracortical inhibition’, which is possibly mediated by GABA_A receptors, is also diminished. Levodopa restores these and other TMS alterations, thus demonstrating that cortical area 4 is sensitive to dopamine modulation. Overall, TMS has provided substantial new pathophysiological insights, which point to a central role of the primary motor cortex in the movement disorder typical of PD. Repetitive (r-)TMS, another form of TMS, has been studied as a treatment for PD motor signs. Although some reports are favorable, others are not, and have raised the problem of appropriate control experiments. Although extremely interesting, the potential therapeutic role of r-TMS in PD needs further evaluation.     

Transcranial magnetic stimulation has no placebo effect on motor learning

ObjectiveMotor learning is the core cognitive function in neurorehabilitation and in various other skill-training activities (e.g. sport, music). Therefore, there is an increasing interest in the use of transcranial magnetic stimulation (TMS) methods for its enhancement. However, although usually assumed, a potential placebo effect of TMS methods on motor learning has never been systematically investigated.MethodsImprovement of performance on the Purdue Pegboard Task over three test-blocks (T0, T1, and T2), separated by >20 min, was used to evaluate motor learning. In Experiment-1, two groups of 10 participants each were compared: one group immediately before T1 received a sham intermittent theta burst stimulation procedure (P-iTBS group), while another did not have any intervention at all (control – CON group). In Experiment-2, a third group of participants (six subjects) who received sham high-frequency repetitive TMS procedure before T1 (P-rTMS group) was compared with P-iTBS group.ResultsAll three groups showed significant learning over time, but without any difference between them, either in Experiment-1 between P-iTBS and CON, or in Experiment-2 between P-rTMS and P-iTBS.ConclusionThe results suggest lack of any placebo effect of TMS on motor learning.SignificanceThe results may help in designing further TMS–motor learning studies and in interpreting their results.     

Transcranial magnetic stimulation in patients with cervical spondylotic myelopathy: Clinical and radiological correlations

Motor evoked potentials (MEPs) were studied in 28 patients with cervical spondylotic myelopathy. MEPs after cortical stimulation were abnormal in 27 patients, the responses in the leg muscles being affected the most often. Clinically asymptomatic motor lesions were detected in 7 patients (25%). The central motor conduction time (CMCT) for the abductor digiti minimi muscles correlated significantly with the clinical disability, whereas the radiological findings did not correlate with the clinical and neurophysiological parameters. In 9 patients MEPs were also recorded in the biceps muscles. The 7 patients with an abnormal CMCT for the biceps muscles had the most severe stenosis at the C-4–C-5 level or higher. The 2 patients with normal MEPs of the biceps muscles both had a stenosis at the C-5–C-6 level. The results of this study suggest that MEPs are useful for detecting spinal cord dysfunction and for localizing the level of the lesion. Some recommendations regarding the possible use of MEPs in the clinical evaluation of patients with cervical spondylotic myelopathy are given. © 1994 John Wiley & Sons, Inc.     

Efficacy of repetitive transcranial magnetic stimulation for Tourette syndrome: A systematic review and meta-analysis

Background

While previous studies have investigated the effect of repetitive transcranial magnetic stimulation (rTMS) in treating Tourette syndrome (TS), the results remain inconclusive.

Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of motor excitability

Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawl of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.     

Repetitive Paired-pulse Transcranial Magnetic Stimulation Over the Visual Cortex Selectively Inhibits Focal Flash VEPs

BackgroundThe human visual system processes different aspects of visual information such as luminance and contrast via multiple channels. We previously used repetitive paired-pulse stimulation (rPPS) over the visual cortex to elicit a disinhibitory effect on the visual recovery function of paired pattern-reversal (PR) visual evoked potentials (VEPs).ObjectiveWe tested the hypothesis that different visual channels exhibit diverse response patterns after rPPS over the visual cortex. Thus, we examined how rPPS influenced each channel of the visual cortex.MethodsWe employed rPPS with a 1.5-ms interstimulus interval over the visual cortex at the stimulus intensity of the visual masking effect. Focal flash (FF) and PR-VEPs (check size, 15 min) were recorded to evaluate the response properties of visual channels in 10 healthy subjects. Visual stimuli were presented for the lower half-field that subtended 6° in radius. The amplitudes and latencies of each VEP were compared before and after rPPS for up to 30 min.ResultsFollowing rPPS, N1-P1 and P1-N2 amplitudes of FF-VEPs decreased linearly up to 30 min. In contrast, the amplitudes of PR-VEPs were not significantly changed. Latencies of FF- and PR-VEPs were also unchanged.ConclusionsModulation of FF-VEPs by rPPS suggests that rPPS selectively induced an inhibitory effect on the luminance channel. Therefore, rPPS may be a promising tool for exploring plastic changes in the visual cortex.     

Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study.

OBJECTIVE: To quantify temperature induced changes (=Uhthoff phenomenon) in central motor conduction and their relation to clinical motor deficits in 20 multiple sclerosis (MS) patients. METHODS: Self-assessment of vulnerability to temperature and clinical examination were performed. We used motor evoked potentials to measure central motor conduction time (CMCT) and applied the triple stimulation technique (TST) to assess conduction failure. The TST allows an accurate quantification of the proportion of conducting central motor neurons, expressed by the TST amplitude ratio (TST-AR). RESULTS: Temperature induced changes of TST-AR were significantly more marked in patients with prolonged CMCT (P=0.037). There was a significant linear correlation between changes of TST-AR and walking velocity (P=0.0002). Relationships were found between pronounced subjective vulnerability to temperature and (i) abnormal CMCT (P=0.02), (ii) temperature induced changes in TST-AR (P=0.04) and (iii) temperature induced changes in walking velocity (P=0.04). CMCT remained virtually unchanged by temperature modification. CONCLUSIONS: Uhthoff phenomena in the motor system are due to varying degrees of conduction block and associated with prolonged CMCT. In contrast to conduction block, CMCT is not importantly affected by temperature. SIGNIFICANCE: This is the first study quantifying the Uhthoff phenomenon in the pyramidal tract of MS patients. The results suggest that patients with central conduction slowing are particularly vulnerable to develop temperature-dependent central motor conduction blocks.