Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial

Individuals with amnestic mild cognitive impairment(aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation(rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS(treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation(sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation(ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China(approval No. BYL20190901) on September 3, 2019 and registered in the Chinese Clinical Trials Registry(registration No. ChiCTR1900028180) on December 14, 2019.     

重复经颅磁刺激对急性脊髓损伤大鼠运动功能的影响

目的 探讨重复经颅磁刺激对急性脊髓损伤大鼠运动功能的影响. 方法 24只SD大鼠按照随机数字表法分为正常组、脊髓损伤对照组(对照组)、脊髓损伤高频磁刺激组(高频组)、脊髓损伤低频磁刺激组(低频组),每组6只.利用重物撞击法制作T10脊髓损伤模型.磁刺激组于手术后24 h开始给予刺激,高频组频率为10Hz,低频组频率为1 Hz,均为阈值刺激.500个脉冲,每天1次,连续4周,脊髓损伤对照组给予假刺激.各组大鼠分别于术后1 d、3d、7d、11 d、14d、21 d、28 d进行BBB行为学评分,于14、28 d时检测运动诱发电位(MEP),应用HE染色观察脊髓组织形态学变化,并应用免疫组织化学法检测神经丝蛋白(NF-200)表达变化. 结果 高频组、低频组大鼠BBB评分明显高于对照组,高频组BBB评分明显高于低频组,差异均有统计学意义(P<0.05).高频组、低频组运动诱发电位潜伏期较短,与对照组、正常组相比差异均有统计学意义(P<0.05);其中高频组较低频组短,差异有统计学意义(P<0.05).高频组、低频组NF-200表达较对照组明显升高,差异均有统计学意义(P<0.05);其中高频组较低频组高,差异有统计学意义(P<0.05).结论 重复经颅磁刺激可以促进脊髓损伤大鼠运动功能的恢复,其机制可能与促进轴突再生有关.高频组较低频组效果明显可能与调节大脑皮层兴奋性有关.     

不同脑部重复经颅磁刺激对精神分裂症患者认知功能的影响

目的:初步探讨不同部位θ短阵快速脉冲(TBS)重复经颅磁刺激(rTMS)对精神分裂症患者认知功能的影响。方法:96例精神分裂症患者随机分为左侧额叶组、双侧额叶组、左侧颞叶组及假刺激组,每组各24例。在维持原有抗精神病药种类及剂量不变的基础上采用TBS模式进行相应部位rTMS,每周5次,4周为1疗程。治疗前后应用威斯康星卡片分类测验-64(WCST-64)、定步调听觉连续加法测验(PASAT)、霍普金斯词汇学习测验-修订版(HVLT-R)对患者认知功能进行评定。结果:92例患者完成疗程;治疗前各组HVLT-R、WCST-64及PASAT评分差异无统计学意义;治疗后,除假刺激组外,其余3组PASAT、HVLT-R评分较治疗前明显升高(P均0.05);WCST-64的持续错误数和持续反应数均明显下降(P0.05,P0.01),其中左侧额叶组及双侧额叶组PASAT、HVLT-R评分较左侧颞叶组明显升高(P0.05,P0.01),WCST-64持续错误数和持续反应数较左侧颞叶组明显下降(P0.05,P0.01),左侧额叶组和双侧额叶组间HVLT-R、WCST-64及PASAT评分差异无统计学意义。结论:TBS模式的rTMS刺激左侧额叶﹑双侧额叶及左侧颞叶对精神分裂症患者认知功能均有明显改善,刺激左侧额叶及双侧额叶的改善作用更佳。     

Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study

BackgroundSeveral factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance).MethodsWe recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate.ResultsA total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups.LimitationsThe number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation.ConclusionOur findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.     

Effects of transcranial direct current stimulation on performance and recovery sleep during acute sleep deprivation: a pilot study

BackgroundPrevious studies claimed that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) improves cognition in neuropsychiatric patients with cognitive impairment, schizophrenia, organic hypersomnia, etc, but few studies evaluated the effects of tDCS on cognitive improvement following sleep deprivation. The objective of this study was to determine whether tDCS (anode on the left DLPFC and cathode on the right DLPFC with a 2-mA current for 30 min) improves cognition following sleep deprivation.MethodsSeven participants received active tDCS and eight participants received sham tDCS when their cognition declined during at least 30 h of sleep deprivation. All participants completed the psychomotor vigilance task, Trail Making Tests A and B, digit cancellation test, Stroop color word test, the Brief Visuospatial Memory Test-Revised and a procedural game every 2 h during the sleep deprivation and after recovery sleep.ResultsCompared to the sham stimulation, active tDCS (anode on the left DLPFC and cathode on the right DLPFC at a 2-mA current for 30 min) had beneficial effects on attention, memory, executive function, processing speed, and the ability to inhibit cognitive interference, and improved in subjective drowsiness and fatigue following sleep deprivation. The lasting effect of a single tDCS on cognition during sleep deprivation was greater than 2 h. In all participants, tDCS did not disturb recovery sleep, and cognitive performance recovered to the baseline levels after recovery sleep.ConclusionsThe study results indicate that tDCS can improve cognition following sleep deprivation and does not disturb recovery sleep or cognitive performance after recovery sleep. The possible pathophysiological mechanisms might be related to the modulation of the corticothalamic pathway. We believe that tDCS can be applied in the treatment of sleep disorders involving sleepiness.Trial registration numberChiCTR2000029420.Date of registration2020-1-31.     

Effects of high-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex on motor recovery in severe hemiplegic stroke: A randomized clinical trial

BackgroundThe contralesional hemisphere compensation may play a critical role in the recovery of stroke when there is extensive damage to one hemisphere. There is little research on the treatment of hemiplegia by high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the contralesional cortex.ObjectiveWe conducted a 2-week randomized, sham-controlled, single-blind trial to determine whether high-frequency rTMS (HF-rTMS) over the contralesional motor cortex can improve motor function in severe stroke patients.MethodsForty-five patients with ischemic or hemorrhagic stroke in the middle cerebral artery territory were randomly assigned to treatment with 10 Hz rTMS (HF group), 1 Hz rTMS (LF group) or sham rTMS (sham group) applied over the contralesional motor cortex (M1) before physiotherapy daily for two weeks. The primary outcome was the change in the Fugl-Meyer Motor Assessment (FMA) Scale score from baseline to 2 weeks. The secondary endpoints included root mean square of surface electromyography (RMS-SEMG), Barthel Index (BI), and contralesional hemisphere cortical excitability.ResultsThe HF group showed a more significant improvement in FMA score (p < 0.05), BI (p < 0.005), contralesional hemisphere cortical excitability and conductivity (p < 0.05), and RMS-SEMG of the key muscles (p < 0.05) compared with the LF group and sham group. There were no significant differences between the LF group and sham group. There was a positive correlation between cortical conductivity of the uninjured hemisphere and recovery of motor impairment (p = 0.039).ConclusionsHF-rTMS over the contralesional cortex was superior to low-frequency rTMS and sham stimulation in promoting motor recovery in patients with severe hemiplegic stroke by acting on contralesional cortex plasticity.Trial registrationClinical trial registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn/showproj.aspx?proj=23264 (ChiCTR-IPR-17013580).     

Effect of cerebellum stimulation on cognitive recovery in patients with Alzheimer disease: A randomized clinical trial

IntroductionEvidence indicates that the cerebellum is involved in cognitive processing. However, the specific mechanisms through which the cerebellum repetitive transcranial magnetic stimulation (rTMS) contributes to the cognitive state are unclear.MethodsIn the current randomized, double-blind, sham-controlled trial, 27 patients with Alzheimer's disease (AD) were randomly allotted to one of the two groups: rTMS-real or rTMS-sham. We investigated the efficacy of a four-week treatment of bilateral cerebellum rTMS to promote cognitive recovery and alter specific cerebello-cerebral functional connectivity.ResultsThe cerebellum rTMS significantly improves multi-domain cognitive functions, directly associated with the observed intrinsic functional connectivity between the cerebellum nodes and the dorsolateral prefrontal cortex (DLPFC), medial frontal cortex, and the cingulate cortex in the real rTMS group. In contrast, the sham stimulation showed no significant impact on the clinical improvements and the cerebello-cerebral connectivity.ConclusionOur results depict that 5 Hz rTMS of the bilateral cerebellum is a promising, non-invasive treatment of cognitive dysfunction in AD patients. This cognitive improvement is accompanied by brain connectivity modulation and is consistent with the pathophysiological brain disconnection model in AD patients.     

Serial repetitive transcranial magnetic stimulation (rTMS) decreases BDNF serum levels in healthy male volunteers

Although repetitive transcranial magnetic stimulation (rTMS) is established in the treatment of depression, there is little knowledge about the underlying molecular mechanisms. In the last decade, the neurotrophic hypothesis of depression entailed a plethora of studies on the role of neurogenesis-associated factors in affective disorders and rTMS treatment. In the present study, we hypothesised a sham-controlled increase of peripheral brain-derived neurotrophic factor (BDNF) levels following serial rTMS stimulations in healthy individuals. We investigated the influence of a cycle of nine daily high-frequency (HF)-rTMS (25 Hz) stimulations over the left dorsolateral prefrontal cortex (DLPFC) on serum levels of BDNF in 44 young healthy male volunteers. BDNF serum concentrations were measured at baseline, on day 5 and on day 10. Overall, the statistical analyses showed that the active and sham group differed significantly regarding their responses of BDNF serum levels. Contrary to our expectations, there was a significant decrease of BDNF only during active treatment. Following the treatment period, significantly lower BDNF serum levels were quantified in the active group on day 10, when compared to the sham group. The participants’ smoking status affected this effect. Our results suggest that serial HF-rTMS stimulations over the left DLPFC decrease serum BDNF levels in healthy male volunteers. This provides further evidence for an involvement of BDNF in clinical rTMS effects.     

Improved executive functioning following repetitive transcranial magnetic stimulation

The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B).     

Cortical plasticity is correlated with cognitive improvement in Alzheimer’s disease patients after rTMS treatment

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has been widely used in non-invasive treatments for different neurological disorders. Few biomarkers are available for treatment response prediction. This study aims to analyze the correlation between changes in long-term potentiation (LTP)-like cortical plasticity and cognitive function in patients with Alzheimer’s disease (AD) that underwent rTMS treatment.MethodsA total of 75 AD patients were randomized into either 20 Hz rTMS treatment at the dorsolateral prefrontal cortex (DLPFC) group (n = 37) or a sham treatment group (n = 38) for 30 sessions over six weeks (five days per week) with a three-month follow-up. Neuropsychological assessments were conducted using the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment-Cognitive Component (ADAS-Cog). The cortical plasticity reflected by the motor-evoked potential (MEP) before and after high-frequency repetitive TMS to the primary motor cortex (M1) was also examined prior to and after the treatment period.ResultsThe results showed that the cognitive ability of patients who underwent the MMSE and ADAS-Cog assessments showed small but significant improvement after six weeks of rTMS treatment compared with the sham group. The cortical plasticity improvement correlated to the observed cognition change.ConclusionsCortical LTP-like plasticity could predict the treatment responses of cognitive improvements in AD patients receiving rTMS intervention. This warrants future clinical trials using cortical LTP as a predictive marker.     

Transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations

BACKGROUND: Neuroimaging studies suggest that auditory hallucinations (AHs) of speech arise, at least in part, from activation of brain areas underlying speech perception. One-hertz repetitive transcranial magnetic stimulation (rTMS) produces sustained reductions in cortical activation. Recent results of 4-day administration of 1-Hz rTMS to left temporoparietal cortex were superior to those of sham stimulation in reducing AHs. We sought to determine if a more extended trial of rTMS could significantly reduce AHs that were resistant to antipsychotic medication. METHODS: Twenty-four patients with schizophrenia or schizoaffective disorder and medication-resistant AHs were randomly allocated to receive rTMS or sham stimulation for 9 days at 90% of motor threshold. Patients receiving sham stimulation were subsequently offered an open-label trial of rTMS. Neuropsychological assessments were administered at baseline and during and following each arm of the trial. RESULTS: Auditory hallucinations were robustly improved with rTMS relative to sham stimulation. Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement. Duration of putative treatment effects ranged widely, with 52% of patients maintaining improvement for at least 15 weeks. Repetitive transcranial magnetic stimulation was well tolerated, without evidence of neuropsychological impairment. CONCLUSIONS: These data suggest that the mechanism of AHs involves activation of the left temporoparietal cortex. One-hertz rTMS deserves additional study as a possible treatment for this syndrome.     

Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Facial Affect Recognition in Schizophrenia

ObjectiveFacial affect recognition, a basic building block of social cognition, is often impaired in schizophrenia. Poor facial affect recognition is closely related to poor functional outcome; however, neither social cognitive impairments nor functional outcome are sufficiently improved by antipsychotic drug treatment alone. Adjunctive repetitive transcranial magnetic stimulation (rTMS) has been shown to enhance cognitive functioning in both healthy individuals and in people with neuropsychiatric disorders and to ameliorate clinical symptoms in psychiatric disorders, but its effects on social cognitive impairments in schizophrenia have not yet been studied. Therefore, we evaluated the effects of sham-controlled rTMS on facial affect recognition in patients with chronic schizophrenia.MethodInpatients (N = 36) on stable antipsychotic treatment were randomly assigned to double-blind high-frequency (10 Hz) rTMS or sham stimulation for a total of ten sessions over two weeks. In the verum group, each session consisted of 10 000 stimuli (20 trains of 5 s) applied over the left dorsolateral prefrontal cortex at 110% of motor threshold. Facial affect recognition was assessed before (T0) and after (T1) the ten sessions.ResultsFacial affect recognition improved significantly more after rTMS (accuracy change: mean = 8.9%, SD = 6.0%) than after sham stimulation (mean = 1.6%, SD = 3.5; Cohen's d = 1.45). There was no correlation with clinical improvement.ConclusionOur results indicate that prefrontal 10 Hz rTMS stimulation may help to ameliorate impaired facial affect recognition in schizophrenia.     

Regular treadmill exercise prevents sleep deprivation-induced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus

Study objectivesEvidence suggests that regular exercise can protect against learning and memory impairment in the presence of insults such as sleep deprivation. The dentate gyrus (DG) area of the hippocampus is a key staging area for learning and memory processes and is particularly sensitive to sleep deprivation. The purpose of this study was to determine the effect of regular exercise on early-phase long-term potentiation (E-LTP) and its signaling cascade in the presence of sleep deprivation.Experimental designRats were exposed to 4 weeks of regular treadmill exercise then subsequently sleep-deprived for 24 h using the modified multiple platform model before experimentation. We tested the effects of exercise and/or sleep deprivation using electrophysiological recording in the DG to measure synaptic plasticity; and Western blot analysis to quantify the levels of key signaling proteins related to E-LTP.Measurements and resultsRegular exercise prevented the sleep deprivation-induced impairment of E-LTP in the DG area as well as the sleep deprivation-associated decrease in basal protein levels of phosphorylated and total α calcium/calmodulin-dependent protein kinase II (P/total-CaMKII) and brain-derived neurotrophic factor (BDNF). High frequency stimulation (HFS) to the DG area was used to model learning stimuli and increased the P-CaMKII and BDNF levels in normal animals: yet failed to change these levels in sleep-deprived rats. However, HFS in control and sleep-deprived rats increased the levels of the phosphatase calcineurin. In contrast, exercise increased BDNF and P-CaMKII levels in exercised/sleep-deprived rats.ConclusionsRegular exercise appears to exert a protective effect against sleep deprivation-induced spatial memory impairment by inducing hippocampal signaling cascades that positively modulate basal and stimulated levels of key effectors such as P-CaMKII and BDNF, while attenuating increases in the protein phosphatase calcineurin.     

Efficacy and safety of simultaneous rTMS–tDCS over bilateral angular gyrus on neuropsychiatric symptoms in patients with moderate Alzheimer's disease: A prospective,randomized, sham-controlled pilot study

BackgroundTreating neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) remains highly challenging. Noninvasive brain stimulation using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) is of considerable interest in this context.ObjectiveTo investigate the efficacy and safety of a novel technique involving simultaneous application of rTMS and tDCS (rTMS–tDCS) over bilateral angular gyrus (AG, P5/P6 electrode site) for AD-related NPS.MethodsEighty-four AD patients were randomized to receive rTMS–tDCS, single-rTMS, single-tDCS, or sham stimulation for 4 weeks, with evaluation at week-4 (W4, immediately after treatment) and week-12 (W12, follow-up period) after initial examination. Primary outcome comprising Neuropsychiatric Inventory (NPI) score and secondary outcomes comprising mini-mental state examination (MMSE), AD assessment scale-cognitive subscale (ADAS-cog), and Pittsburgh sleep quality index (PSQI) scores were collected and analyzed by a two-factor (time and treatment), mixed-design ANOVA.ResultsrTMS–tDCS produced greater improvement in NPI scores than single-tDCS and sham at W4 and W12 (both P < 0.017) and trended better than single-rTMS (W4: P = 0.058, W12: P = 0.034). rTMS–tDCS improved MMSE scores compared with single-tDCS at W4 (P = 0.011) and sham at W4 and W12 (both P < 0.017). rTMS–tDCS also significantly improved PSQI compared with single-rTMS and sham (both P < 0.017). Interestingly, rTMS–tDCS-induced NPI/PSQI improvement was significantly associated with MMSE/ADAS-cog improvement. tDCS- and/or rTMS-related adverse events appeared slightly and briefly.ConclusionsrTMS–tDCS application to bilateral AG can effectively improve AD-related NPS, cognitive function, and sleep quality with considerable safety.     

High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking

BACKGROUND: The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine. Recently, acute high-frequency repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans. For this reason, we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by studying rTMS effects on craving and cigarette smoking. METHOD: Fourteen treatment-seeking smokers were included in a double-blind crossover trial, conducted in 2002, comparing single days of active versus sham stimulation. Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence. RESULTS: High-frequency (20-Hz) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly (p <.01) in an active stimulation compared with sham stimulation. Levels of craving did not change significantly. CONCLUSION: High-frequency rTMS may be useful for treatment in smoking cessation.     

Effects of high-frequency repetitive transcranial magnetic stimulation on reducing hemiplegic shoulder pain in patients with chronic stoke: a randomized controlled trial

Objective: To examine whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS), applied over the primary motor cortex of the affected hemisphere, could be used to manage hemiplegic shoulder pain (HSP).

Methods: Twenty-four chronic stroke patients with chronic HSP, randomly assigned into the rTMS group (10 sessions of high-frequency stimulation) or the sham group (sham stimulation), were performed. The Numeric Rating Scale (NRS) was used to evaluate the intensity of pain at pretreatment, and at 1 day, and 1, 2 and 4 weeks after treatment. Changes in upper-limb motor function were evaluated using the Motricity Index (MI-UL) and modified Brunnstrom Classification (MBC).

Results: When compared to pretreatment, the rTMS group showed a significant decrease in the NRS score at 1 day, and 1, 2 and 4 weeks after finishing rTMS sessions, with no significant change in the sham group. The NRS score after the rTMS sessions reduced by 30.1% at 1 day, 29.3% at 1 week, 28.0% at 2 weeks and 25.3% at 4 weeks. Passive shoulder range of motion, MI-UL, and MBC, however, did not significantly change in either group.

Conclusions: High-frequency rTMS could be used as a safe, beneficial therapeutic tool to manage HSP. We think it can be used as an adjuvant therapeutic modality to enhance the therapeutic outcome of HSP.     

Transcranial Magnetic Stimulation Combined with Speech and Language Training in Early Aphasia Rehabilitation: A Randomized Double-Blind Controlled Pilot Study

Abstract

Background: Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere, which hypothetically reflects a maladaptive strategy of brain reorganization. Objective: We investigated whether repetitive transcranial magnetic stimulation (rTMS) inhibiting the right-hemisphere homologue of Broca’s area improves language restitution if combined with speech/language therapy. Methods: Forty aphasic patients during the subacute phase of ischemic stroke were randomized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS. Naming, repetition, and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline, immediately after therapy, and 15 weeks after completing treatment. Results: Although language functions improved in both experimental and control groups after 3 weeks, only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants. Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition. Conclusions: Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients, although it might benefit selected patients.     

Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients

Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.     

The influence of high-frequency repetitive transcranial magnetic stimulation on endogenous estrogen in patients with disorders of consciousness

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been proposed as a promising therapeutic intervention for neurological disorders. However, the precise mechanisms of rTMS in neural excitability remains poorly understood. Estradiol is known to have strong influence on cortical excitability. This study aimed to determine whether high-frequency (HF) rTMS influences endogenous estradiol in male patients with disorders of consciousness (DOC).MethodsA randomized controlled trial was conducted with a total of 57 male patients with DOC. Eventually, 50 patients completed the study. Twenty-five patients underwent real rTMS, and 25 patients underwent sham rTMS, which were delivered over the dorsolateral prefrontal cortex. The primary outcome measure was the change in serum estradiol from baseline to after 10 sessions of HF-rTMS. The improvement in the total score of the JFK Coma Recovery Scale-Revised (CRS-R) was also assessed.ResultsChanges in estradiol levels and CRS-R scores from pre-to post-treatment were significantly different between the active rTMS and sham stimulation conditions. A significant enhancement of CRS-R scores in the patients receiving rTMS stimulation was observed compared to the sham group. Serum estradiol levels in patients following HF-rTMS were significantly higher than their baseline levels, whereas no significant changes were found in the sham group from pre-to post-stimulation. The rise in estradiol levels was greater in responders than in non-responders. The changes in estradiol levels were significantly positively correlated with the improvement in CRS-R scores.ConclusionThese preliminary findings indicate that serum estradiol levels are affected by HF-rTMS and positively related to clinical responses in male patients with DOC. The elevation of estradiol levels may lay a physiological foundation for successful rTMS treatment for DOC patients by increasing cortical excitability.     

Double-blind,randomized, placebo controlled trial on the effect of 10 days low-frequency rTMS over the vertex on sleep in Parkinson’s disease

ObjectiveA recent report indicates repetitive transcranial magnetic stimulation (rTMS) improves sleep in Parkinson’s disease (PD). The aim of this work is to evaluate the effect of 10 days rTMS on sleep parameters in PD patients.MethodsDouble-blind, placebo-controlled design. Eighteen idiopathic PD patients completed the study. Sleep parameters were evaluated through actigraphy and the Parkinson’s Disease Sleep Scale (PDSS), along with depression (Hamilton Depression Rating Scale, HDS), and the Unified Parkinson’s Disease Rating Scale (UPDRS). Evaluations were carried out before treatment with rTMS (pre-evaluation, PRE), after the rTMS treatment programme (post-evaluation, POST), and one week after POST (POST-2). Nine PD patients received real rTMS and the other 9 received sham rTMS daily for 10 days, (100 pulses at 1 Hz) applied with a large circular coil over the vertex.ResultsStimulation had no effect over actigraphic variables. Conversely PDSS, HDS, and UPDRS were significantly improved by the stimulation. Notably, however, these changes were found equally in groups receiving real or sham stimulation.ConclusionsrTMS, using our protocol, has no therapeutic value on the sleep of PD patients, when compared to appropriate sham controls. Future works assessing the possible therapeutic role of rTMS on sleep in PD should control the effect of placebo.