Short-term cortical plasticity in patients with dystonia: a study with repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold (RMT) intensity produces a progressive facilitation of motor-evoked potential (MEP) amplitude that outlasts the end of stimulation. This phenomenon is related to a short-term enhancement of cortical excitatory interneurones. In this study, we investigated whether 5 Hz-rTMS elicits similar MEP facilitation during stimulation and similar facilitatory after-effects in patients with upper limb dystonia and healthy subjects. Trains of 5, 10, and 20 stimuli were delivered at 120% RMT over the primary motor cortex with the subjects at rest. rTMS-trains were followed by single test stimuli delivered at various interstimulus intervals (0.5-10 s) at 120% RMT using a conditioning-test paradigm. Single conditioning stimuli were also delivered. The effects of suprathreshold 1 Hz-rTMS were also tested. The MEP amplitude during the course of the trains and of the test stimuli was measured. In control experiments, we investigated the role of the afferent inputs elicited by muscle twitches after ulnar nerve stimulation on the MEP amplitude. In patients and healthy subjects, MEP amplitude increased significantly during the course of 5 Hz-trains. In both groups the MEP facilitation outlasted the end of 5 Hz-rTMS, however the facilitatory after-effects were more pronounced and lasted longer in patients than in healthy subjects. MEP amplitudes during and after 1 Hz-rTMS remained unchanged. Ulnar nerve stimulation did not change the test MEP amplitude. We conclude that in patients with upper limb dystonia there is an abnormal recovery from MEP facilitation after suprathreshold 5 Hz-rTMS suggesting an abnormal pattern of short-term cortical plasticity.     

Usefulness of repetitive transcranial magnetic stimulation as a maintenance treatment in patients with major depression

Objectives: To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS), venlafaxine or a combination of both treatments as a maintenance treatment in patients with treatment-resistant depression (TRD).

Methods: In a three-arm open-label study, 66 patients, including 45 remitters, who responded to rTMS (n?=?25), venlafaxine (n?=?22), or a combination of both treatments (n?=?19) continued to receive the treatment that led to a response as a maintenance treatment over 12 months. Maintenance rTMS was administered twice per week for 1 month, once per week for 2 months, and once every 2 weeks for 9 months. Venlafaxine was maintained at the dose that induced a clinical response (150 or 225?mg/day).

Results: After the 12-month follow-up, the rates of remitters (HDRS?2?=^?1.25; P?=?.3). The rates of patients who not relapsed (HDRS?2?=^?0.33; P?=?.8): 40.0% in the rTMS group, 45.1% in the venlafaxine group and 36.9% in the combination group.

Conclusions: The three maintenance approaches exhibited similar efficacies in relapse prevention and the maintenance of remission in patients with TRD.     

Human cortical theta reactivity to high-frequency repetitive transcranial magnetic stimulation

Electroencephalography (EEG) can directly monitor the temporal progression of cortical changes induced by repetitive Transcranial Magnetic Stimulation (rTMS) and facilitate the understanding of cortical and subcortical influences in the genesis of oscillations. In this combined rTMS/EEG study, we aimed to investigate changes in oscillatory activity after high-frequency (～11 Hz) rTMS relative to the number of applied pulses. Twenty intermittent trains of 20 or 60 rTMS pulses were delivered over the human primary motor cortex at rest and tuned to individual mu frequency. The regional and interregional oscillatory neural activity after stimulation were evaluated using event-related power (ERPow) and event-related coherence (ERCoh) transformations. The most prominent changes for ERPow were observed in the theta band (4-7 Hz), as an increase in ERPow up to 20 s following 60 rTMS pulses, whereas ERPow increases were smaller in mu (10-12 Hz) and beta (13-30 Hz). ERCoh revealed that rTMS 60 modulated the connectivity in the theta band for up to 20 s. The topography of mu and theta changes were not identical; mu was more focal and theta was more global. Our data suggested the presence of independent cortical theta and mu generators with different reactivity to rTMS but could not rule out possible thalamocortical contributions in generating theta and mu over the motor network.     

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a new therapeutic tool in epilepsy, where it can be used to suppress seizures or treat comorbid conditions such as mood disorder. However, as rTMS carries a risk of inducing seizures among other adverse events, its safety and tolerability in the population with epilepsy warrant distinct consideration, as this group is especially seizure-prone. Accordingly, we performed a review of the literature to estimate the risk of seizures and other adverse events associated with rTMS in patients with epilepsy. We performed an English-language literature search, and reviewed all studies published from January 1990 to February 2007 in which patients with epilepsy were treated with rTMS, and complemented the literature search with personal correspondence with authors when necessary. We identified 30 publications that described patients with epilepsy who underwent rTMS, and noted total number of relevant subjects, medication usage, incidence of adverse events, and rTMS parameters including stimulus frequency, number of stimuli, train duration, intertrain interval, coil type, and stimulation sites. The data were analyzed for adverse events related to rTMS. Crude per-subject risk, as well as per-subject mean risk weighted by sample size and risk per 1000 stimuli weighted by number of stimuli in each study, were computed for seizures and for other adverse events. Adverse events or lack thereof was reported in 26 studies (n=280 subjects). Adverse events attributed to rTMS were generally mild and occurred in 17.1% of subjects. Headache was most common, occurring in 9.6%. The most serious adverse event was seizure during treatment, which occurred in four patients (1.4% crude per-subject risk). All but one case were the patients' typical seizures with respect to duration and semiology, and were associated with low-frequency rTMS. A single case of an atypical seizure appearing to arise from the region of stimulation during high-frequency rTMS is reported. No rTMS-related episodes of status epilepticus were reported. We cautiously conclude that the risk of seizure in patients with epilepsy undergoing rTMS is small, and the risk of other mild adverse events is comparable to that seen when rTMS is used to treat other diseases. Status epilepticus or life-threatening seizures have not been reported in patients undergoing rTMS treatment. rTMS thus appears to be nearly as safe in patients with epilepsy as in nonepileptic individuals, and warrants further investigation as a therapy in this population.     

重复经颅磁刺激治疗偏头痛患者的临床研究

目的观察重复经颅磁刺激(rTMS)治疗偏头痛的疗效和安全性。方法入选的96例偏头痛患者分为rTMS组和假刺激组,每组48例,并记录患者一般资料。rTMS组患者接受经颅磁刺激治疗,隔日1次,15次为一疗程,并进行随访。假刺激组使用伪线圈,不产生治疗效应。记录头痛频率改善、视觉模拟评分量表(VAS)评分改善情况、临床疗效和不良反应等。结果与假刺激组相比,rTMS组患者在头痛发作频率和VAS改善以及临床疗效上均有所好转,差异有统计学意义(P<0.05)。随访过程中rTMS组3例患者出现头晕乏力,但均未发生严重不良反应。结论 tTMS治疗偏头痛是有效且相对安全的方法。     

Increased migraine-free intervals with multifocal repetitive transcranial magnetic stimulation

IntroductionEpisodic migraine is a debilitating condition associated with vast impairments of health, daily living, and life quality. Several prophylactic treatments exist, having a moderate ratio of action related to side effects and therapy costs. Repetitive transcranial magnetic stimulation (rTMS) is an evidence based therapy in several neuropsychiatric conditions, showing robust efficacy in alleviating specific symptoms. However, its efficacy in migraine disorders is unequivocal and might be tightly linked to the applied rTMS protocol. We hypothesized that multifocal rTMS paradigm could improve clinical outcomes in patients with episodic migraine by reducing the number of migraine days, frequency and intensity of migraine attacks, and improve the quality of life.MethodsWe conducted an experimental, double-blind, randomized controlled study by applying a multifocal rTMS paradigm. Patients with episodic migraine with or without aura were enrolled in two centers from August 2018, to December 2019, and randomized to receive either real (n = 37) or sham (sham coil stimulation, n = 28) multifocal rTMS for six sessions over two weeks. Patients, physicians, and raters were blinded to the applied protocol. The experimental multifocal rTMS protocol included two components; first, swipe stimulation of 13 trains of 140 pulses/train, 67 Hz, 60% of RMT, and 2s intertrain interval and second, spot burst stimulation of 33 trains of 15 pulses/train, 67 Hz, 85% of RMT, and 8s intertrain interval. Reduction >50% from the baseline in migraine days (as primary outcome) and frequency and intensity of migraine attacks (as key secondary outcomes) over a 12-week period were assessed. To balance the baseline variables between the treatment arms, we applied the propensity score matching through the logistic regression.ResultsAmong 65 randomized patients, sixty (age 39.7 ± 11.6; 52 females; real rTMS n = 33 and sham rTMS n = 27) completed the trial and five patients dropped out. Over 12 weeks, the responder's rate in the number of migraine days was significantly higher in the real rTMS compared to the sham group (42% vs. 26%, p < 0.05). The mean migraine days per month decreased from 7.6 to 4.3 days in the real rTMS group and from 6.2 to 4.3 days in the sham rTMS group, resulting in a difference with real vs. sham rTMS of −3.2 days (p < 0.05). Similarly, over the 12-week period, the responder's rate in the reduction of migraine attacks frequency was higher in the real rTMS compared to the sham group (42% vs 33%, p < 0.05). No serious adverse events were observed.ConclusionOur pilot study shows compelling evidence in a double placebo-controlled trial that multifocal rTMS is an effective and well-tolerated preventive treatment in patients with episodic migraine.     

Experience with transcranial magnetic stimulation in cortical mapping

Abstract

Seventeen subjects underwent transcranial magnetic stimulation (TMS) toward cortical mapping. Cortical mapping produced scalp representations of five upper extremity muscles and their spatial orientation tended to support an expected anatomic pattern. Muscle map locations and map areas showed trends across musical skill and hand dominance as well. No subject experienc.ed adverse effects during the study. TMS promises to be an effective tool for noninvasive cortical mapping. [Neural Res 1997; 19: 435-440]     

Slow right prefrontal transcranial magnetic stimulation as a treatment for medication-resistant depression: a double-blind, placebo-controlled study

Over the past decade, efforts have been made to assess the positive therapeutic effects of transcranial magnetic stimulation (TMS) by altering the excitability of the brain. We conducted a double-blind, placebo-controlled study to assess the efficacy of right prefrontal slow repetitive TMS in patients with treatment refractory major depression. This pilot study supports the therapeutic potential of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the treatment of refractory major depression. Additional studies will be necessary to assess the efficacy of rTMS with different indices (frequency, intensity, and stimulation site) for major depression and other psychiatric diseases.     

重复经颅磁刺激用于精神分裂症中安全性及可行性

目的探讨重复经颅磁刺激用于精神分裂症中安全性及可行性。方法运用随机抽样方选取我院2013-01-2014-09收治的60例精神分裂症患者,依据治疗方法将患者分为研究组(n=30)和对照组(n=30)。对照组患者给予假刺激方案治疗,研究组给予重复经颅磁刺激治疗。结果研究组阳性和阴性症状评分均显著低于对照组(P0.05),精神症状改善时间和住院时间均显著短于对照组(P0.05),治疗的总有效率93.3%(28/30)显著高于对照组70.0%(21/30)(P0.05),不良反应发生率13.3%(4/30)显著低于对照组33.3%(10/30),P0.05。结论重复经颅磁刺激用于精神分裂症中安全可行,值得推广。     

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.     

重复经颅磁刺激联合帕利哌酮对精神分裂症患者认知功能的影响

目的 探讨重复经颅磁刺激(rTMS)联合帕利哌酮缓释片对精神分裂症患者认知功能的疗效及安全性.方法 选择符合入组条件的首发精神分裂症患者61名,随机分成治疗组30例(帕利哌酮缓释片联合rTMS),对照组31例(单纯药物).分别于治疗前及治疗4周后应用阳性与阴性症状量表(PANSS)评定临床症状;应用数字划消测验(CT)...     

In-session seizures during low-frequency repetitive transcranial magnetic stimulation in patients with epilepsy

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool for patients with intractable epilepsy. Although seizures during treatment have been reported as adverse events in some patients, the nature and severity of seizures that may be provoked by low-frequency rTMS in patients with epilepsy have not been extensively studied. Accordingly, this article documents seizures in patients (n = 5) with intractable epilepsy and average seizure frequency greater than one per day who underwent 1-Hz rTMS for seizure suppression. We report three observations in the present case series: (1) in each instance the in-session seizure was typical in semiology to the patient’s habitual seizures, (2) the duration of each documented seizure was either the same as or shorter than the patients’ baseline seizures, and (3) the overall neurological outcome on follow-up was not affected by the in-session seizures. More data will be required for valid conclusions with respect to safety and tolerability of low-frequency rTMS in patients with epilepsy, but it is noteworthy from our perspective that seizures during rTMS in this series were similar to the patients’ habitual seizures, occurred in patients with epilepsy with baseline seizure frequency exceeding one per day, and did not correlate with a poor neurological outcome or with absence of clinical response to rTMS.     

Motor cortical excitability studied with repetitive transcranial magnetic stimulation in patients with Huntington's disease.

OBJECTIVE: TMS techniques have provided controversial information on motor cortical function in Huntington's disease (HD). We investigated the excitability of motor cortex in patients with HD using repetitive transcranial magnetic stimulation (rTMS). METHODS: Eleven patients with HD, and 11 age-matched healthy subjects participated in the study. The clinical features of patients with HD were evaluated with the United Huntington's Disease Rating Scale (UHDRS). rTMS was delivered with a Magstim Repetitive Magnetic Stimulator through a figure-of-8 coil placed over the motor area of the first dorsal interosseus (FDI) muscle. Trains of 10 stimuli were delivered at 5 Hz frequency and suprathreshold intensity (120% resting motor threshold) with the subjects at rest and during voluntary contraction of the target muscle. RESULTS: In healthy subjects at rest, rTMS produced motor evoked potentials (MEPs) that increased in amplitude over the course of the trains. Conversely in patients, rTMS left the MEP size almost unchanged. In both groups, during voluntary contraction rTMS increased the silent period (SP) duration. CONCLUSIONS: Because rTMS modulates motor cortical excitability by activating cortical excitatory and inhibitory interneurons these findings suggest that in patients with HD the excitability of facilitatory intracortical interneurones is decreased. SIGNIFICANCE: We suggest that depressed excitability of the motor cortex in patients with HD reflects a disease-related weakening of cortical facilitatory mechanisms.     

低频重复经颅磁刺激治疗首发青少年抑郁症的临床对照研究

目的 探讨低频重复经颅磁刺激(rTMS)治疗首发青少年抑郁症的疗效及安全性.方法 将30例首发未用药的青少年抑郁症患者随机分为rTMS组和对照组各15例,均不采用药物治疗.rTMS组采用低频rTMS刺激右侧额叶背外侧皮质(DLPFC),对照组采用假性刺激,每周治疗5次,连续治疗2周.采用汉密尔顿抑郁量表24项(HAMD24)评估治疗前后的疗效.结果 (1)rTMS组有效率100%,对照组有效率0%,两组差异有统计学意义(P<0.01).(2)治疗后rTMS组HAMD24总分及因子分均较基线期显著下降(P<0.05),对照组HAMD24总分及因子分较基线期无明显变化(P>0.05).(3)rTMS组和对照组的不良反应发生率差异无统计学意义(P>0.05),两组均未出现严重不良反应.结论 低频rTMS可有效改善首发青少年抑郁症,有较好的安全性.     

The use of transcranial magnetic stimulation in cognitive neuroscience: A new synthesis of methodological issues

Transcranial magnetic stimulation (TMS) has become a mainstay of cognitive neuroscience, thus facing new challenges due to its widespread application on behaviorally silent areas. In this review we will summarize the main technical and methodological considerations that are necessary when using TMS in cognitive neuroscience, based on a corpus of studies and technical improvements that has become available in most recent years. Although TMS has been applied only relatively recently on a large scale to the study of higher functions, a range of protocols that elucidate how this technique can be used to investigate a variety of issues is already available, such as single pulse, paired pulse, dual-site, repetitive and theta burst TMS. Finally, we will touch on recent promising approaches that provide powerful new insights about causal interactions among brain regions (i.e., TMS with other neuroimaging techniques) and will enable researchers to enhance the functional resolution of TMS (i.e., state-dependent TMS). We will end by briefly summarizing and discussing the implications of the newest safety guidelines.     

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     

Neural correlates of high frequency repetitive transcranial magnetic stimulation improvement in post-stroke non-fluent aphasia: A case study

Damage to the left inferior frontal gyrus (lIFG) affects language and can cause aphasia in stroke. Following left hemisphere damage it has been suggested that the homologue area in the right hemisphere compensates for lost functions. An increasing number of studies have demonstrated that inhibitory 1-Hz repetitive transcranial magnetic stimulation (rTMS) targeting the right IFG can be useful for enhancing recovery in aphasic patients. In the present study we applied activating high frequency (10-Hz) rTMS, which increases cortical excitability, to the damaged lIFG daily for 3 weeks. Pre- and post-TMS EEG are performed, as well as language function assessments with the Aachener Aphasia Test Battery. Results demonstrate a decrease in rIFG activity post rTMS and normalization for the lIFG for beta3 frequency band. Also increased activity was in the right supplementary motor area for beta3 frequency band. In comparison to pre-TMS the aphasic patient improved on repetition tests, for naming and comprehension. After rTMS increased functional connectivity was shown in comparison to before between the lIFG and the rIFG for theta and beta3 frequency band. This case report suggests that 10 Hz rTMS of the lIFG can normalize activity in the lIFG and right IFG possibly mediated via altered functional connectivity.