rTMS Of Motor Cortex Research Articles

Primary motor cortex functionally contributes to language comprehension: An online rTMS study

Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words – an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension.

The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders.

Background:Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome.Methods:Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients’ psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome.Results:The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013–0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000–0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome.Conclusion:We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders.

Neuromodulatory effects of offline low-frequency repetitive transcranial magnetic stimulation of the motor cortex: A functional magnetic resonance imaging study.

Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) can modulate cortical excitability and is thought to influence activity in other brain areas. In this study, we investigated the anatomical and functional effects of rTMS of M1 and the time course of after-effects from a 1-Hz subthreshold rTMS to M1. Using an “offline” functional magnetic resonance imaging (fMRI)-rTMS paradigm, neural activation was mapped during simple finger movements after 1-Hz rTMS over the left M1 in a within-subjects repeated measurement design, including rTMS and sham stimulation. A significant decrease in the blood oxygen level dependent (BOLD) signal due to right hand motor activity during a simple finger-tapping task was observed in areas remote to the stimulated motor cortex after rTMS stimulation. This decrease in BOLD signal suggests that low frequency subthreshold rTMS may be sufficiently strong to elicit inhibitory modulation of remote brain regions. In addition, the time course patterns of BOLD activity showed this inhibitory modulation was maximal approximately 20 minutes after rTMS stimulation.

Daily Repetitive Transcranial Magnetic Stimulation for Poststroke Upper Limb Paresis in the Subacute Period

We conducted a randomized, double-blind, sham-controlled study to assess the efficacy in motor recovery and safety of daily repetitive transcranial magnetic stimulation (rTMS) in subacute stroke patients. Forty-one patients were randomly assigned to a real or sham stimulation group. Each patient underwent regular rehabilitation accompanied by a series of 10 daily 5-Hz rTMS of the ipsilesional primary motor cortex (M1) or sham stimulation. The primary outcome was motor recovery evaluated by the Brunnstrom stages (BS). The secondary outcomes were improvement in the Fugl-Meyer Assessment (FMA), grip power, National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), a quantitative measurement of finger tapping movement, and the incidence of adverse events. Thirty-nine patients completed the study and were included in the analyses. The real rTMS group demonstrated additional improvement in the BS hand score at the last follow-up compared to the sham. The grip power, the NIHSS motor score, and the number of finger taps in the affected hand improved in the real stimulation group but not in the sham group. The BS upper limb scores, the FMA distal upper limb score, the NIHSS total score, and the FIM motor score showed improvement from baseline at the earlier time points after the real rTMS. There were no additional improvements in the other scores after the real rTMS compared to the sham. No serious adverse events were observed. Our results suggest that dailyhigh-frequency rTMS of the ipsilesional M1 is tolerable and modestly facilitates motor recovery in the paralytic hand of subacute stroke patients.

69. Prolonged inhibitory effect of 1 Hz rTMS of the motor cortex on the nociceptive evoked potentials to contralateral hand stimulation

High frequency motor cortex rTMS produces an inhibitory effect on pain, however there are only few data about the effect of low frequency motor cortex rTMS on clinical and experimental pain. Since low frequency rTMS should have an inhibitory effect on motor cortex, whose activation reduces experimental pain, one could expect that 1 Hz motor cortex rTMS increases objective pain measures, such as laser evoked potentials (LEPs). In 8 healthy subjects, we investigated the effect of 1 Hz rTMS of left motor cortex on LEPs to stimulation of both right and left hand dorsum. LEPs were recorded at 4 different times: baseline, Time 0 (immediately after 20 min of 1 Hz rTMS), Time +20 (20 min after 1 Hz rTMS), Time +40 (40 min after 1 Hz rTMS). rTMS modified the amplitude of N2/P2 LEP component only to right hand stimulation ( F = 12.06, p F = 0.7, p = 0.56). Post-hoc analysis showed that the N2/P2 amplitude was reduced at Time 0, Time +20, and Time +40, as compared to baseline ( p

RTMS and disorders of the motor system

Recent guidelines of the IFCN (Lefaucheur et al., 2014) on the therapeutic use of rTMS list the are variety of diseases. Here the focus will be laid on movement disorders, stroke and ALS. No recommendation for the antiparkinsonian effect can be made for high frequency (HF) or low frequency (LF) rTMS of the hand representation in M1 and for HF rTMS of the SMA. Only a possible antiparkinsonian effect of HF rTMS of bilateral (multiple) sites in M1 (Level C) emerged from this meta-analysis. A probable antidepressant effect of HF rTMS of the left DLPFC in Parkinson’s disease (Level B) emerged from the literature analysis. In motor stroke a possible effect of LF rTMS of the contralesional motor cortex in (post-)acute motor stroke (Level C) and a probable effect of LF rTMS of the contralesional motor cortex in chronic motor stroke (Level B) emerged. Ipsilesional stimulation revealed only possible effects of HF rTMS of the ipsilesional motor cortex in (post-)acute motor stroke and of HF rTMS of the ipsilesional motor cortex in chronic motor stroke (Level C). No recommendation can be made for ALS. Possible pitfalls for negative studies are mentioned combined with suggestions for improved study designs.

ID 156 – Prolonged inhibitory effect of 1 Hz rTMS of the motor cortex on the nociceptive evoked potentials to contralateral hand stimulation

High frequency motor cortex rTMS produces an inhibitory effect on pain, however there are only few data about the effect of low frequency motor cortex rTMS on clinical and experimental pain. Since low frequency rTMS should have an inhibitory effect on motor cortex, whose activation reduces experimental pain, one could expect that 1 Hz motor cortex rTMS increases objective pain measures, such as laser evoked potentials (LEPs). In 8 healthy subjects, we investigated the effect of 1 Hz rTMS of left motor cortex on LEPs to stimulation of both right and left hand dorsum. LEPs were recorded at 4 different times: baseline, Time 0 (immediately after 20 min of 1 Hz rTMS), Time +20 (20 min after 1 Hz rTMS), Time +40 (40 min after 1 Hz rTMS). rTMS modified the amplitude of N2/P2 LEP component only to right hand stimulation (F = 12.06, p < 0.001), while there was no effect on left hand LEPs (F = 0.7, p = 0.56). Post-hoc analysis showed that the N2/P2 amplitude was reduced at Time 0, Time +20, and Time +40, as compared to baseline (p < 0.01). Conversely of what expected, 1 Hz rTMS of the motor cortex inhibits contralateral pain; this effects last up to 40 min after the cortical stimulation.

ID 99 – Functional connectivity study on repetitive transcranial magnetic stimulation for central post-stroke pain

Objective Central post-stroke pain (CPSP) is one of the most refractory chronic pain syndromes. We and others have reported that repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex relieves pain in patients with CPSP. However, the mechanism underlying the pain relief remains unclear. This study aimed to investigate functional connectivity specific to CPSP and functional connectivity alteration associated with pain relief by rTMS. Methods Subjects were 12 patients with CPSP and 12 age-matched healthy controls. Resting-state function MRI (rs-fMRI) was taken before and after 5 Hz-rTMS of the ipsilesional primary motor cortex in patients, meanwhile rs-fMRI was taken once in controls without the rTMS intervention. rs-fMRI data was preprocessed, and second-level analyses of seed-to-voxel connectivity were implemented. Results The functional connectivity related to the ipsilesional primary motor cortex (FC-M1) was larger in patients than in controls. The alteration of FC-M1 after rTMS negatively correlated with pain relief. Conclusions Our findings suggested that alteration of the functional connectivity might be one of the mechanisms underlying pain relief by rTMS in CPSP. Key message rTMS might affect the functional connectivity related to the stimulation site in patients with CPSP.

Bilateral low frequency rTMS of the primary motor cortex may not be a suitable treatment for levodopa-induced dyskinesias in late stage Parkinson's disease

BackgroundIn late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS), delivered at the primary motor cortex (MC) or the supplementary motor area (SMA), may reduce levodopa-induced dyskinesias (LID), either in a single or a multiple session stimulation protocol. In our current clinical research, we examined whether single or multiple (accelerated) sham-controlled bilateral LF rTMS session(s) applied to the primary motor cortices are able to reduce levodopa-induced dyskinesias in patients with advanced Parkinson's disease. MethodsDuring a levodopa challenge test, we first investigated the effect of a single sham-controlled session of LF rTMS (1 Hz) to both left and right primary motor cortical areas on dyskinesias and motor function in nine late-stage Parkinson patients. In a second study, patients were assigned to a five day sham-controlled bilateral motor cortex cross-over accelerated LF rTMS protocol and effects on dyskinesias, motor and executive function and emotional status were assessed. ResultsWe found no significant clinical change in levodopa-induced dyskinesias and motor function with either stimulation protocol. ConclusionsOne or multiple bilateral LF rTMS session(s) applied to the primary motor cortex were unable to reduce levodopa-induced dyskinesias in late-stage Parkinson patients.

High-Frequency Repetitive Transcranial Magnetic Stimulation Reduces Pain in Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is one of the most intractable pain disorders, especially in elderly patients. There is evidence that repetitive transcranial magnetic stimulation (rTMS) reduces neuropathic pain; however, its effectiveness for PHN is unknown. This study investigated the efficacy of high-frequency rTMS in patients with PHN. A total of 40 patients were randomly assigned to receive 10 sessions of real or sham rTMS of the primary motor cortex. Each stimulation session consisted of a series of 300 five-second pulses with a frequency of 10 Hz and an interval of 3 seconds between each train, giving a total of 1500 pulses per session. The primary outcome was pain intensity measured before stimulation from first intervention (T0) to the final stimulation (T10), and 1 and 3 months after final stimulation (T11 and T12). Other outcomes measured included scores on the short form McGill pain questionnaire, self-rating depression scale, quality of life (QOL), sleep quality, the patient global impression of change, medication regulation, and reported adverse events. The real rTMS group demonstrated greater reduction of visual analogue scale (VAS) than the sham group at each time point except for T0 (P = 0.399) and T1 (P = 0.091). Mean VAS reduction in the real rTMS group was 16.89% for duration of disease longer than 6 months. These analgesic effects were associated with long-term improvement in rating-scale items related to QOL. The results suggest that rTMS is an effective and safe therapy in patients with PHN.

From pulses to pain relief: an update on the mechanisms of rTMS-induced analgesic effects.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action.

Motor cortex rTMS improves dexterity in relapsing-remitting and secondary progressive multiple sclerosis.

The motor cortex (MC) receives an excitatory input from the cerebellum which is reduced in patients with cerebellar lesions. High-frequency repetitive transcranial magnetic stimulation (rTMS) induces cortical facilitation which can counteract the reduced cerebellar drive to the MC. Our study included 24 relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients with dysmetria. The patients were divided into two groups: Group A received two sessions of real MC rTMS and Group B received one session of real rTMS and one session of sham rTMS. Ten healthy volunteers formed group C. Evaluation was carried out using the nine-hole pegboard task and the cerebellar functional system score (FSS) of the expanded disability status scale (EDSS). Group A patients showed a significant improvement in the time required to finish the pegboard task (P=0.002) and in their cerebellar FSS (P=0.000) directly after the second session and 1month later. The RRMS patients showed more improvement than the SPMS patients. Group B patients did not show any improvement in the pegboard task or the cerebellar FSS. These results indicate that MC rTMS can be a promising option in treating both RRMS or SPMS patients with cerebellar impairment and that its effect can be long-lasting.

Not an Aspirin: No Evidence for Acute Anti-Nociception to Laser-Evoked Pain After Motor Cortex rTMS in Healthy Humans

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown efficacy in relieving neuropathic pain. Whether its analgesic effect also applies to acute physiological nociception remains unclear due to previous contradictory findings. To provide an in-depth investigation of the effects of motor cortex HF-rTMS on acute laser-evoked pain and excitability of nociceptive networks in healthy subjects. Randomized, placebo-controlled, double-blind, cross-over study in 20 healthy participants. Laser heat stimuli at nociceptive threshold were delivered to the right hand, allowing assessment of: (a) subjective pain intensity and unpleasantness; (b) laser-evoked potentials (LEPs, 128 electrodes) and their source model; (c) sympathetic skin responses, and (d) spino-thalamic pathway excitability. Data were collected before and 20 minutes after a session of neuro-navigated 20 Hz rTMS to the contralateral motor cortex. Subjective pain reports to thermal laser pulses, amplitude of late cortical potentials and sympathetic skin responses were decreased after cortical stimulation, to a similar extent whether it was active or placebo. Early cortical potentials and nociceptive network excitability remained identical before and after rTMS, as did anatomical sources of LEPs. Our results do not provide evidence for a genuine anti-nociceptive effect of rTMS on acute physiological pain. We suggest that motor cortex rTMS may act upon high-order networks linked to the emotional and cognitive appraisal of chronic pain, and/or modulate pathologically sensitized networks, rather than change the physiological transmission within an intact nervous system. Such dichotomy is reminiscent of that observed with most drugs used for neuropathic pain.

Enhancement of Neuromodulation with Novel Pulse Shapes Generated by Controllable Pulse Parameter Transcranial Magnetic Stimulation.

Standard repetitive transcranial magnetic stimulation (rTMS) devices generate bidirectional biphasic sinusoidal pulses that are energy efficient, but may be less effective than monophasic pulses that induce a more unidirectional electric field. To enable pulse shape optimization, we developed a controllable pulse parameter TMS (cTMS) device. We quantified changes in cortical excitability produced by conventional sinusoidal bidirectional pulses and by three rectangular-shaped cTMS pulses, one bidirectional and two unidirectional (in opposite directions), and compared their efficacy in modulating motor evoked potentials (MEPs) produced by stimulation of motor cortex. Thirteen healthy subjects completed four sessions of 1Hz rTMS of the left motor cortex. In each session, the rTMS electric field pulse had one of the four shapes. Excitability changes due to rTMS were measured by applying probe TMS pulses before and after rTMS, and comparing resultant MEP amplitudes. Separately, we measured the latency of the MEPs evoked by each of the four pulses. While the three cTMS pulses generated significant mean inhibitory effects in the subject group, the conventional biphasic cosine pulses did not. The strongest inhibition resulted from a rectangular unidirectional pulse with dominant induced current in the posterior-anterior direction. The MEP latency depended significantly on the pulse shape. The pulse shape is an important factor in rTMS-induced neuromodulation. The standard cosine biphasic pulse showed the smallest effect on cortical excitability, while the greatest inhibition was observed for an asymmetric, unidirectional, rectangular pulse. Differences in MEP latency across the various rTMS pulse shapes suggest activation of distinct subsets of cortical microcircuitry.

Crossed inhibition of sensory cortex by 0.3 Hz transcranial magnetic stimulation of motor cortex.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of motor cortex causes persistent inhibitory effects in the targeted area. rTMS of motor cortex impairs sensory perception and results in a persistent change in cortical function at remote sites. The ability of rTMS to induce sustained changes in cortical function has led to studies testing its therapeutic efficacy in neurologic disorders, including epilepsy. Studies on the effect of low-frequency rTMS of motor cortex on the contralateral motor cortex have provided evidence for both inhibitory and excitatory changes. This study was designed to determine the effect of low-frequency rTMS of the right motor cortex on the contralateral sensory cortex. Before and after 0.3-Hz rTMS of right motor cortex, perception of ipsilateral threshold of cutaneous stimuli was assessed and somatosensory evoked potentials (SEPs) recorded after stimulation of the right thumb in eight normal subjects. In a control group of six subjects, sensory responses were assessed after rTMS anterior to the right motor cortex. After rTMS of motor cortex, detection of threshold sensory stimuli decreased by more than 50% compared with pre-rTMS (P < 0.05). The change in sensory perception lasted at least 30 minutes. No change was detected in the control group. Amplitude of the N20-P25 waveform of the SEP decreased from a mean of 0.84 muV before rTMS to 0.54 muV immediately after rTMS of motor cortex (P < 0.05). 0.3 Hz rTMS of motor cortex inhibits the contralateral sensory cortex.

Transcranial magnetic stimulation of the brain

Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvard's Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIH's PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials.

Repetitive transcranial magnetic stimulation once a week induces sustainable long-term relief of central poststroke pain.

Central poststroke pain is a serious problem for some patients after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been reported to relieve poststroke pain but its efficacy is still controversial. We tested the possibility that rTMS, when applied once a week, would induce sustainable relief of poststroke pain. Eighteen patients with central poststroke pain were included in this study. rTMS (10 trains of 10-sec 5 Hz-rTMS) was delivered over the primary motor cortex on the affected side. The rTMS session was repeated once a week for 12 weeks, and for six patients the intervention was continued for one year. The degree of the pain was assessed before each weekly rTMS session to evaluate sustainable effects. The effects of the rTMS reached a plateau at the eighth week. At the 12th week, the rTMS was effective in 61.1% of the patients; 5 of the 18 patients showed more than 70% reduction based on a visual analog scale, 6 patients showed 40-69% reduction, and 7 remained at a pain reduction level of less than 40%. When patients were divided into two groups with or without severe dysesthesia, it was found that eight patients with severe dysesthesia showed less pain relief than those without. In the six patients who continued rTMS for one year, the pain relief effects also were sustained. Although this was an open-label study without a control group, our findings suggest that rTMS of the primary motor cortex, when maintained once a week, could help to relieve poststroke pain.

Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease (PD). However, results evaluating the effectiveness of rTMS in PD are mixed, mostly owing to low statistical power or variety in individual rTMS protocols. To determine the rTMS effects on motor dysfunction in patients with PD and to examine potential factors that modulate the rTMS effects. Databases searched included PubMed, EMBASE, Web of Knowledge, Scopus, and the Cochrane Library from inception to June 30, 2014. Eligible studies included sham-controlled, randomized clinical trials of rTMS intervention for motor dysfunction in patients with PD. Relevant measures were extracted independently by 2 investigators. Standardized mean differences (SMDs) were calculated with random-effects models. Motor examination of the Unified Parkinson's Disease Rating Scale. Twenty studies with a total of 470 patients were included. Random-effects analysis revealed a pooled SMD of 0.46 (95% CI, 0.29-0.64), indicating an overall medium effect size favoring active rTMS over sham rTMS in the reduction of motor symptoms (P<.001). Subgroup analysis showed that the effect sizes estimated from high-frequency rTMS targeting the primary motor cortex (SMD, 0.77; 95% CI, 0.46-1.08; P<.001) and low-frequency rTMS applied over other frontal regions (SMD, 0.50; 95% CI, 0.13-0.87; P=.008) were significant. The effect sizes obtained from the other 2 combinations of rTMS frequency and rTMS site (ie, high-frequency rTMS at other frontal regions: SMD, 0.23; 95% CI, -0.02 to 0.48, and low primary motor cortex: SMD, 0.28; 95% CI, -0.23 to 0.78) were not significant. Meta-regression revealed that a greater number of pulses per session or across sessions is associated with larger rTMS effects. Using the Grading of Recommendations, Assessment, Development, and Evaluation criteria, we characterized the quality of evidence presented in this meta-analysis as moderate quality. The pooled evidence suggests that rTMS improves motor symptoms for patients with PD. Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects. The findings of our meta-analysis may guide treatment decisions and inform future research.

一次運動野刺激による中枢性脳卒中後疼痛患者の機能的結合

We have previously reported the efficacy of 5 Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in relief of central post–stroke pain (CPSP). The objective of this study was to explore changes of functional connectivity related to CPSP condition, and to assess changes of functional connectivity induced by rTMS in patients with CPSP. In 14 patients with CPSP and 14 control subjects, resting–state functional MRI were taken. Twelve of these patients received 5 Hz–rTMS of M1, and underwent resting–state functional MRI before and after rTMS. Functional connectivity associated with motor and default mode networks increased in patients with CPSP compared with control subjects. Moreover, functional connectivity associated with default mode network and anterior cingulate cortex decreased after rTMS. These findings suggest that several functional networks are involved in pathophysiology of CPSP and mechanisms of action of rTMS.

A pilot study on the effects of low frequency repetitive transcranial magnetic stimulation on lower extremity spasticity and motor neuron excitability in patients after stroke

To evaluate the effect of low frequency, repetitive transcranial magnetic stimulation (rTMS) on the lower extremity spasticity and motor neuron excitability in patients after stroke. Seven patients after stroke aged 42-78 years were included in this pretest-posttest clinical trial. The rTMS at 1 Hz and duration of 20 min was applied to the intact leg motor cortex for five consecutive sessions. Primary outcome measures were the Modified Modified Ashwoth Scale (MMAS) and the H(max)/M(max) ratio. Measurements were taken at baseline (T0), after the last treatment (5th) session (T1), and at 1 week follow up (T2). Clinically assessed ankle plantar flexor spasticity (p = 0.05) improved significantly after treatment at T1. Knee extensor spasticity scored 0 after treatment at T1 and T2. The H(max)/M(max) ratio showed no statistically significant improvement after treatment. The pilot data indicate that the inhibitory rTMS of the intact leg motor cortex in patients after stroke may improve the lower extremity spasticity.