Baseline effective connectivity predicts response to repetitive transcranial magnetic stimulation in patients with treatment-resistant depression

Repetitive transcranial magnetic stimulation (rTMS) has become a popular treatment option for treatment-resistant depression (TRD). However, suboptimal response rates highlight the need for improved efficacy through optimisation of treatment protocol and patient selection. We investigate whether the limbic salience network and its connectivity with prefrontal stimulation sites predict immediate and longer-term responsiveness to rTMS. Twenty-seven patients with TRD were randomly allocated to receive 16 sessions of either conventional rTMS or intermittent theta-burst (iTBS) over 4 weeks; delivered using connectivity profiling and neuronavigation to target person-specific dorsolateral prefrontal cortex (DLPFC). At baseline and 3-month follow-up, patients underwent clinical assessment and scanning session, and 1-month clinical follow-up. Resting-state fMRI data were entered into seed-based functional and effective connectivity analyses between right anterior insula (rAI) and DLPFC target, and independent components analysis to extract resting-state networks. Cerebral blood flow (CBF) was also assessed in the rAI. All brain measures were compared between baseline and follow-up, and related to treatment response at 1- and 3-months. Baseline fronto-insular effective connectivity and salience network connectivity were significantly positively correlated, while baseline rAI CBF was negatively correlated, with early (1-month) response to rTMS treatment but not sustained response (3-months), suggesting persistence of therapeutic response is not associated with baseline features. Connectivity or CBF measures did not change between the two time points. We demonstrate that fronto-insular and salience-network interactions can predict early response to rTMS in TRD, suggesting that these network nodes may be key regions toward developing rTMS response biomarkers.     

重复经颅磁刺激治疗对抑郁症患者自杀态度的影响

目的探讨重复经颅磁刺激治疗对抑郁症患者自杀态度的影响。方法将本院住院的抑郁症患者中,有自杀倾向的40例随机分成两组,药物组及r TMS治疗组各20例。采用IAT测验、自杀态度问卷、汉密尔顿抑郁自评量表及贝克自杀意念量表的测试分别在治疗前、治疗12周后对两组患者进行测定,评定自杀态度总分(SA)、IAT效应值(D)、抑郁分值和一周自杀倾向得分,以及外显与内隐态度的影响,评估r TMS治疗抑郁症患者自杀态度的临床疗效。结果两组治疗后与治疗前D值比较有统计学意义(P<0.05);SA、抑郁分及自杀倾向比较差异显著(P<0.05);r TMS治疗组与药物治疗组在治疗前后SA及自杀倾向比较差异具有统计学意义(P<0.05),而D值与抑郁分比较无统计学意义(P>0.05)。结论抑郁症伴有自杀倾向的患者在药物持续治疗的基础上,给予r TMS治疗,显著改善患者睡眠障碍,减少负面思想活动、自杀倾向及自杀态度明显改善。     

A transcranial magnetic stimulation study of the effects of olanzapine and risperidone on motor cortical excitability in patients with schizophrenia

RATIONALE: There has been a progressive increase in interest in the functioning of the main inhibitory and excitatory neurotransmitters in the pathophysiology of schizophrenia. Limited information is available as to how these neurotransmitters are affected by commonly prescribed antipsychotic agents. OBJECTIVES: We investigated whether the atypical antipsychotics olanzapine and risperidone differ in their effects on inhibitory and excitatory cortical markers measured with transcranial magnetic stimulation. METHODS: Electromyographic recordings from the abductor pollicis brevis muscle were made during focal transcranial magnetic stimulation to the contralateral motor cortex and during bilateral cortical stimulation. Twenty patients on each drug and 22 controls were studied with measures of the resting motor threshold, motor evoked potential size, post-excitatory silent period duration, cortical inhibition and facilitation to paired-pulse transcranial magnetic stimulation and transcallosal inhibition. RESULTS: The patient groups differed from the controls in the silent period and transcallosal inhibition measures, both of which assess cortical inhibitory activity. The two medication groups differed in the magnitude of the resting motor threshold and several measures of transcallosal inhibition that reflect the spread of inhibitory activity between hemispheres. CONCLUSIONS: These findings suggest that olanzapine and risperidone differ subtly in their effects on cortical inhibitory mechanisms. Further evaluation is required to establish whether these differences may reflect or underlie differences seen between these medications in their clinical profiles, including their effects on cognitive symptoms of schizophrenia.     

A meta-analysis of repetitive transcranial magnetic stimulation in the treatment of depression

Repetitive transcranial magnetic stimulation (rTMS) is an emerging potential treatment for depression, but the data supporting its efficacy have not been systematically reviewed. The purpose of this study was to conduct a meta-analysis of rTMS trials in the treatment of depression. A search for all published and unpublished sham-controlled studies of left or right prefrontal cortical rTMS in the treatment of depression evaluated by the Hamilton Depression Rating Scale (HDRS) was conducted using no language restrictions. Fixed- and random-effects meta-analyses were performed on 12 studies comparing the decrease in HDRS scores achieved with rTMS and sham stimulation. Initial results with a fixed-effects analysis failed homogeneity testing; thus, a random-effects analysis was used to calculate all results. In 12 studies (16 individual effect sizes), the weighted mean effect size was 0.81 (95% CI: 0.42-1.20, P < .001). For studies using left dorsolateral pre-frontal cortex (DLPFC) stimulation (11 studies, 14 effect sizes), the weighted mean effect size was 0.89 (95% CI: 0.44-1.35, P < .001). For studies using left DLPFC stimulation in a parallel-groups design (seven studies, nine effect sizes), the weighted mean effect size was 0.88 (95% CI: 0.22-1.54, P < .01). No study showed a mean decrease in HDRS scores of > 50%, and the number of responders to rTMS (defined as a > 50% decrease in HDRS scores) across studies was relatively small (13.7% with rTMS versus 7.9% with sham stimulation). rTMS is statistically superior to sham stimulation in the treatment of depression, showing a moderate to large effect size. However, the clinical significance of these results is modest. The differences in response to rTMS across studies are not clearly explained, and, therefore, more research is needed.     

Plasma concentrations of neuroactive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression.

There is evidence for altered levels of neuroactive steroids in major depression that normalize after successful antidepressant pharmacotherapy. Currently it is not known whether this is a general principle of clinically effective antidepressant therapy or a pharmacological effect of antidepressants. Here, we investigated whether repetitive transcranial magnetic stimulation (rTMS) may affect plasma concentrations of neuroactive steroids in a similar way as antidepressant pharmacotherapy. Progesterone, 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta- tetrahydroprogesterone (3alpha,5beta-THP), 3beta,5alpha-tetrahydroprogesterone (3beta, 5alpha-THP) and dehydroepiandrosterone (DHEA) were quantified in 37 medication-free patients suffering from a major depressive episode before and after 10 sessions of left prefrontal rTMS. Plasma samples were analyzed by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. There was a significant reduction of depressive symptoms after rTMS. However, plasma concentrations of neuroactive steroids were not affected by rTMS and not related to clinical response. Clinical improvement after extended daily treatment with rTMS is not accompanied by changes in neuroactive steroid levels. Changes in neuroactive steroid levels after antidepressant pharmacotherapy more likely reflect specific pharmacological effects of antidepressant drugs and are not necessary for the amelioration of depressive symptoms.     

文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效比较

目的 :比较文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效及安全性。方法 :文拉法辛组2 6例 ,用文拉法辛 50～ 2 0 0mg·d- 1,po ,bid～tid ;氯米帕明组 2 4例 ,用氯米帕明 50～ 2 0 0mg·d- 1,po ,bid～tid ;2组均以HAMD ,HAMA ,TESS评定观察 6wk。结果 :对抑郁症状的治疗 ,文拉法辛组与氯米帕明组显效率均为 84 % (P >0 .0 5) ;对伴随的焦虑症状的治疗 ,文拉法辛组显效率为 92 % ,氯米帕明组显效率为 63% (P <0 .0 5)。文拉法辛组常见不良反应为恶心 ( 2 7% )、口干 ( 19% )、便秘( 19% )、震颤 ( 12 % )、乏力 ( 8% )、头晕 ( 8% )等。结论 :文拉法辛治疗抑郁症伴焦虑症状的疗效肯定、耐受性良好 ,而且对焦虑症状的治疗效果优于氯米帕明     

Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation

This review focused on the treatment-emergent mania/hypomania (TEM) associated with repetitive transcranial magnetic stimulation (rTMS) treatment of depression. English-language literature published from 1966-2006 and indexed in Medline was searched. Ten of 53 randomized controlled trials on rTMS treatment of depression specifically addressed TEM. The pooled TEM rate is 0.84% for the active treatment group and 0.73% for the sham group. The difference is not statistically significant. Along with case reports, a total of 13 cases of TEM associated with rTMS treatment of depression have been published. Most of these patients were diagnosed with bipolar disorder and the majority of patients experiencing TEM took medication concurrent with rTMS. The parameters of rTMS used in these cases were scattered over the spectrum of major parameters explored in previous studies. Most train durations and intervals were within the published safety guidelines of the field. Reducing the frequency of sessions from two per day to one per day might be associated with a lower likelihood of TEM recurrence. The severity of manic symptoms varied significantly, but all cases responded to treatment that included a decrease or discontinuation of antidepressant and/or rTMS treatment and/or use of anti-manic medication. Current data suggests that rTMS treatment carries a slight risk of TEM that is not statistically higher than that associated with sham treatment. More systematic studies are needed to better understand TEM associated with rTMS. Special precautions and measures should be adopted to prevent, monitor, and manage TEM in research and practice.     

Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity.

Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to substantial antidepressant effects in the majority of prior clinical studies. As effect sizes and stimulation conditions have varied greatly, controversy persists regarding effective stimulation parameters (e.g. intensity, frequency, localization). In the present controlled study, we investigated whether the antidepressant efficacy of rTMS may be related to the stimulation intensity applied. Thirty-one patients suffering from a pharmacotherapy-resistant major depressive episode were randomly assigned to three treatment groups receiving rTMS at different stimulation intensities: (1) intensity at the individual motor threshold (MT); (2) 90% subthreshold intensity; and (3) low intensity of standard sham rTMS. Each patient underwent 10 sessions of 10 Hz rTMS with 1500 stimuli/day over the left dorsolateral prefrontal cortex. Improvement of depressive symptoms after rTMS significantly increased with stimulation intensity across the three groups. A 30% to 33% reduction of baseline depression scores was observed after rTMS at MT intensity. Similarly, groups differed significantly regarding the clinical course after rTMS with the lowest number of antidepressant interventions and the shortest hospital stay in the MT intensity group. These findings support the hypothesis of a relationship between stimulation intensity of rTMS and its antidepressant efficacy.     

重复经颅磁刺激联合米氮平治疗首发抑郁症的临床观察

目的探讨重复经颅磁刺激联合米氮平治疗首发抑郁症的疗效及安全性。方法将63例首发抑郁症的患者随机分为治疗组和对照组,治疗组33例,对照组30例。两组均应用米氮平片30mg／d治疗,治疗组在应用米氮平治疗的基础上联合重复经颅磁刺激治疗,刺激左额叶前部背外侧,每周5次,共治疗20次;对照组应用伪刺激线圈,刺激部位、次数、频率同治疗组,有振动声音,但不产生磁场效应。分别于治疗前及治疗后第1、2、4周末应用汉密尔顿抑郁量表（HAMD）、副反应量表（TESS）评价临床疗效和副反应。结果两组均完成治疗,治疗后第2周末两组患者的HAMD评分与治疗前比较,差异有统计学意义（P〈0．05或P〈0．01）;治疗组在治疗第1周末即显示出明显疗效,与对照组比较差异有统计学意义（P〈0．05）。治疗组总有效率（97％）与对照组总有效率（90％）比较,差异有统计学意义（P〈0．05）。两组均未出现明显的副反应。结论重复经颅磁刺激联合米氮平治疗首发抑郁症起效快,能增强抗抑郁效果,耐受性好。     

脑卒中患者应用康复训练联合重复经颅磁刺激治疗的效果分析

目的评价康复训练联合重复经颅磁刺激治疗对脑卒中患者心理障碍及神经功能缺损的影响。方法选取河南科技大学第一附属医院2019年4月至2021年3月接收的脑卒中患者88例进行随机对照试验, 按随机数字表法分为参照组与联合组, 各44例。参照组中, 男24例, 女20例, 年龄49～83(64.3±5.2)岁, 应用康复训练治疗;联合组中, 男25例, 女19例, 年龄50～83(64.7±5.0)岁, 应用康复训练联合重复经颅磁刺激治疗。对比两组患者治疗前后心理障碍、神经功能和日常生活能力改善情况, 并采用SPSS 19.0处理数据, 组间比较采用t检验、χ2检验。结果治疗前, 两组患者抑郁、焦虑等心理障碍评分比较, 差异均无统计学意义(均P>0.05);治疗后, 联合组抑郁评分为(53.78±3.33)分、焦虑评分为(47.67±4.94)分, 参照组分别为(57.46±4.29)分、(53.05±4.83)分, 联合组抑郁、焦虑评分均低于参照组(t=4.495、5.165, 均P<0.001)。治疗前, 联合组神经功能、日常生活能力评分比较, 差异均无统计学意义(均P>...     

神经病理性疼痛重复经颅磁刺激治疗研究进展

神经病理性疼痛是一类由躯体感觉神经系统(外周和中枢神经系统)损伤或疾病而产生的疼痛,临床上表现为自发性疼痛、痛觉过敏、异常疼痛和感觉异常等特征,严重影响患者及其家属的正常生活.神经病理性疼痛的常见类型包括三叉神经痛、幻肢痛、糖尿病性神经痛、疱疹后神经痛、脊髓损伤后疼痛和脑卒中后疼痛等,减轻患者的疼痛、使之早日恢复正常生活是治疗的首要目标.本文简述重复经颅磁刺激治疗神经病理性疼痛的机制以及治疗部位、方案、疗程等.     

Interleaved transcranial magnetic stimulation/functional MRI confirms that lamotrigine inhibits cortical excitability in healthy young men.

Little is known about how lamotrigine (LTG) works within brain circuits to achieve its clinical effects. We wished to determine whether the new technique of interleaved transcranial magnetic stimulation (TMS)/functional magnetic resonance imaging (fMRI) could be used to assess the effects of LTG on activated motor or prefrontal/limbic circuits. We carried out a randomized, double-blind, crossover trial involving two visits 1 week apart with TMS measures of cortical excitability and blood oxygen level-dependent TMS/fMRI. Subjects received either a single oral dose of 325 mg of LTG or placebo on each visit. In all, 10 subjects provided a complete data set that included interleaved TMS/fMRI measures and resting motor threshold (rMT) determinations under both placebo and LTG conditions. A further two subjects provided only rMT data under the two drug conditions. LTG caused a 14.9+/-9.6% (mean+/-SD) increase in rMT 3 h after the drug, compared with a 0.6+/-10.9% increase 3 h after placebo (t=3.41, df =11, p<0.01). fMRI scans showed that LTG diffusely inhibited cortical activation induced by TMS applied over the motor cortex. In contrast, when TMS was applied over the prefrontal cortex, LTG increased the TMS-induced activation of limbic regions, notably the orbitofrontal cortex and hippocampus. These results suggest that LTG, at clinically relevant serum concentrations, has a general inhibitory effect on cortical neuronal excitability, but may have a more complex effect on limbic circuits. Furthermore, the interleaved TMS/fMRI technique may be a useful tool for investigating regional brain effects of psychoactive compounds.     

不同频率重复经颅磁刺激对改善亚急性期缺血性脑卒中患者吞咽功能的研究

目的研究不同频率重复经颅磁刺激(rTMs)在治疗亚急性期缺血性脑卒中患者吞咽功能障碍的作用。方法选取2016年10月～2018年5月在中山市人民医院康复医学科治疗的90例缺血性脑卒中患者,按随机数字表法分成高频rTMS组、低频rTMS组和对照组各30例。在常规药物治疗及功能训练相同的情况下,高频rTMS组、低频rTMS组给予每天1次、每次20min的高频(5Hz)或低频(1Hz)rTMS治疗,连续14d,比较3组患者治疗前后的洼田饮水试验分级、SSA评分和sEMG值。结果治疗前3组患者间比较差异无统计学意义(P 0.05)。治疗后,三组患者的洼田饮水试验分级、SSA评分和sEMG值均较治疗前改善,差异有统计学意义(P 0.05);高频rTMS组、低频rTMS组的吞咽功能恢复明显优于对照组,洼田饮水试验分级、SSA评分和sEMG值与对照组比较差异均有统计学意义(P 0.05),高频rTMS组与低频rTMS组间洼田饮水试验分级、SSA评分和sEMG值比较差异无统计学意义(P 0.05)。结论高频及低频rTMS均有利于缺血性脑卒中患者吞咽功能的康复,且两者间疗效无明显差异。     

Priming stimulation enhances the effectiveness of low-frequency right prefrontal cortex transcranial magnetic stimulation in major depression

OBJECTIVES: Low-frequency, right-sided repetitive transcranial magnetic stimulation (rTMS) to the prefrontal cortex has been shown to have antidepressant effects. Recent research has suggested that preceding low-frequency rTMS with a period of low-intensity, 6-Hz stimulation ("priming") enhances the physiological effects of low-frequency stimulation. The aim of this study was to investigate whether priming stimulation would enhance therapeutic response to low-frequency rTMS in patients with depression. METHOD: The study consisted of a 2-arm, double-blind, randomized, controlled trial in 60 patients with treatment-resistant depression. Right 1-Hz rTMS was provided in one continuous, 15-minute train to all subjects. The priming stimulation (twenty 5-second, 6-Hz trains) or an equivalent, sham preceded 1-Hz stimulation. The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: There was a significant overall reduction in MADRS scores across the 4 weeks of the study and a significantly greater reduction in MADRS scores in the active-priming group compared with the sham-priming group. CONCLUSIONS: Low-intensity, high-frequency priming stimulation appears to enhance the response to low-frequency, right-sided rTMS treatment in patients with treatment-resistant depression.     

盐酸帕罗西汀联合重复经颅磁刺激对产后抑郁症患者MMSE评分及生活质量的影响分析

目的分析探讨盐酸帕罗西汀联合重复经颅磁刺激对产后抑郁症患者MMSE评分及生活质量的影响。方法回顾分析2016年5月~2018年6月期间收治产后抑郁症患者120例,按治疗方式分对照组(60例接受盐酸帕罗西汀治疗)和研究组(60例接受盐酸帕罗西汀联合重复经颅磁刺激治疗),比较两组治疗效果,如MMSE评分、生活质量等。结果治疗前组间MMSE评分比较差异无统计学意义(P>0.05),治疗后,研究组MMSE评分高于对照组,差异有统计学意义(P<0.05)。治疗前组间SCL-90评分比较差异无统计学意义(P>0.05),治疗后,研究组SCL-90评分高于对照组(P<0.05)。结论可用盐酸帕罗西汀联合重复经颅磁刺激治疗产后抑郁症,可显著改善其认知功能和生活质量。     

Partial clinical response to 2 weeks of 2 Hz repetitive transcranial magnetic stimulation to the right parietal cortex in depression

The aim of this treatment study was to evaluate the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) over the right parietal cortex in depression. In a double-blind, sham-controlled design ten consecutive sessions of 2 Hz rTMS (inter-pulse interval 0.5 s) at 90% motor threshold to the right parietal cortex (2400 pulses per session) were applied to 34 patients with the primary diagnosis of DSM-IV depression and a score of > or =15 on the 17-item Hamilton Rating Scale for Depression (HAMD). The primary outcome measures were the percentage change from baseline on the 17-item HAMD scores after ten sessions, and the percentage of clinical (defined as > or =50% reduction in HAMD score) and partial clinical (defined as > or =30% reduction in HAMD score) responders. Reduction of HAMD scores in the real rTMS treatment (mean real+/-S.D., -19.9+/-32.5%) was not statistically different from the sham rTMS treatment (mean sham+/-S.D., -5.6+/-28.4%), and the number of clinical responders did not differ between treatments. However, a significant greater number of partial clinical responders were observed in the real (43.8%) compared to the sham rTMS treatment (6.3%). This study provides the first evidence showing that 2 Hz rTMS over the right parietal cortex may have antidepressant properties, and warrants further research.     

Effect of electroconvulsive therapy in repetitive transcranial magnetic stimulation non-responder MDD patients: a preliminary study

The aim of this study was to measure the effectiveness of ECT in-patients who had failed to respond to a course of repetitive transcranial magnetic stimulation (rTMS) treatment. Seventeen patients with severe MDD who had not responded to a course of rTMS were switched to receive ECT treatments. All the patients were assessed with the Hamilton Rating Scale for Depression, the Global Assessment Functioning Scale, the Global Depression Scale, and the Pittsburgh Sleep Quality Index. Response to the treatment was defined as a 50% decrease in HDRS final score and a final GAS higher than 60. Seven out of 17 patients responded to ECT. Three out of 5 non-psychotics and 4 out of 12 psychotic patients responded. ECT seems to be an effective treatment for 40% of patients who failed to respond to rTMS treatment. Whether this is a result of reduced responsiveness to ECT in rTMS-resistant patients or a consequence of small sample size requires further study.     

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression

There is growing interest worldwide in rTMS as a clinical treatment for depression. Apart from efficacy, its safety as a clinical treatment must be considered before its widespread use can be advocated. All published, sham-controlled rTMS depression trials were reviewed for reported side-effects and outcomes of formal neuropsychological testing. In addition, all reports of seizures occurring with rTMS were reviewed. Other safety concerns (effects on hearing; headache, pain, induced currents in electrical circuits, histotoxicity, electromagnetic field exposure, psychiatric complications, safety in pregnancy) are discussed. Common side-effects were of a minor nature, e.g. headache. There was a low incidence of accidental seizures and induced hypomania, both of which were associated with identified risk factors for which subjects should be screened. Long-term effects of repeated rTMS sessions are as yet unknown. When given within recommended guidelines, the overall safety profile of rTMS is good, and supports its further development as a clinical treatment.