重复经颅磁刺激与无抽搐电休克联合度洛西汀治疗难治性抑郁症对照研究

目的探讨重复经颅磁刺激(rTMS)与无抽搐电休克(MECT)联合度洛西汀治疗难治性抑郁症的疗效和安全性。方法将难治抑郁症患者60例随机分为rTMS组(rTMS+度洛西汀)30例和MECT组(MECT+度洛西汀)30例,2组均观察治疗8周,治疗前及治疗2、4、8周末用汉密尔顿抑郁量表(HAMD-24)进行评分,以减分率评定疗效。采用副反应量表(TESS)评价不良反应。结果治疗2周末MECT组HAMD总分减分率显著大于rTMS组(P0.05),4周末、8周末2组减分率差异无统计学意义(P0.05)。结论 rTMS与MECT联合度洛西汀治疗难治性抑郁症疗效相当,且rTMS组不良反应相对较轻。     

人格对伴认知功能障碍患者认知功能的影响

目的本文研究人格特质对抑郁症伴认知功能障碍患者的认知功能的影响。方法对研究对象进行汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)、蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)的筛查及艾森克人格问卷(Eysenck Personality Questionnaire,EPQ)、认知功能如威斯康星卡片分类测验(Wisconsin Card Sorting Test,WCST)、韦氏成人智力量表(Wechsler Adult Intelligence Scale,WAIS)、韦氏记忆量表(Wechsler Memory Scale,WMS)的评定。结果病例组精神质(Psychoticism,P)、神经质(Neuroticism,N)性人格得分高于健康组,而外向性(Extraversion,E)人格得分两组无明显差异。HAMD总分、人格及人格与抑郁的交互作用对抑郁症认知功能有影响。结论抑郁症伴认知功能障碍患者的人格特质一方面可直接影响其认知功能,另一方面还可通过与抑郁程度的交互作用影响认知功能,调节抑郁程度及认知之间的关系。     

低频重复经颅磁刺激联合度洛西汀治疗难治性抑郁症的疗效

目的探讨低频重复经颅磁刺激(rTMS)联合度洛西汀对难治性抑郁症的疗效。方法将符合CCMD-3抑郁症诊断标准,至少应用两种不同作用机制抗抑郁药足量、足疗程治疗无效的43例患者随机分为研究组(n=22例)和对照组(n=21例)。研究组给予低频(≤1Hz)rTMS联合度洛西汀治疗,对照组单用度洛西汀治疗,观察6周。2组分别于治疗前和治疗2、4、6周末应用汉密尔顿抑郁量表(HAMD)评定疗效,采用症状量表(TESS)评定2组不良反应。结果 2组在治疗6周后HAMD评分较治疗前均有显著下降(P<0.05),研究组在治疗2、4、6周HAMD总分显著低于对照组(P<0.05或P<0.01)。2组不良反应发生率比较差异无统计学意义(P>0.05)。结论低频rTMS合并度洛西汀治疗难治性抑郁症显效快,早期能显著改善患者重度抑郁情绪,疗效优于单一用药,不良反应发生率低,安全性高。     

高频重复经颅磁刺激合并艾司西酞普兰治疗老年难治性抑郁症对照研究

目的 探讨高频重复经颅磁刺激（rTMS）合并艾司西酞普兰对老年难治性抑郁症的治疗价值和安全性.方法 将70例老年抑郁症患者随机分为研究组和对照组各35例,两组患者均服用艾司西酞普兰15 mg/d,疗程4周;研究组合并rTMS治疗.治疗前后使用汉密尔顿抑郁量表（HAMD）、贝克抑郁量表（BDI）、大体功能评定量表（GAF）及匹茨堡睡眠质量指数量表（PSQI）评定疗效.结果 研究组有效率高于对照组（x2=6.97,P＜0.01）.研究组治疗4周后GAF量表评分与治疗前比较显著升高（P＜0.01）,而BDI、HAMD、PSQI量表评分均明显下降（P＜0.01）;对照组治疗4周后HAMD、PSQI量表评分与治疗前比较明显下降（P＜0.01）.治疗后GAF量表研究组评分显著高于对照组（P＜0.01）;而BDI、HAMD、PSQI量表评分研究组显著低于对照组（P＜0.01）.结论 高频重复经颅磁刺激合并艾司西酞普兰治疗老年难治性抑郁症效果明显,无明显不良反应.     

重复经颅磁刺激治疗精神分裂症阴性症状的随机双盲研究

目的探讨重复经颅磁刺激（rTMS）治疗精神分裂症阴性症状的疗效。方法 30例精神分裂症患者被随机分为rTMS真刺激组（治疗组,15例）和rTMS伪刺激组（对照组,15例）,采用θ短阵快速脉冲刺激（TBS）模式刺激左侧前额叶背外侧皮质（DLPFC）,每周5次,共干预20次。于基线、治疗2周及治疗4周时应用阳性与阴性症状量表（PANSS）的阴性因子分和阴性症状量表（SANS）进行疗效评定。结果共有27例患者完成研究,对照组有3例脱落。经rTMS干预4周后,治疗组与对照组的PANSS阴性因子分减分值分别为（4.67±2.47）分和（2.33±1.87）分,两组比较有统计学差异（z=-2.41,P=0.016）;SANS总分减分值分别为（11.87±8.04）分和（5.92±6.47）分,两组比较有统计学差异（z=2.08,P=0.038）。根据PANSS阴性因子分评定,治疗组的有效率达到46.7%,对照组的有效率为16.7%;根据SANS总分评定治疗组的有效率达到46.7%,而对照组的有效率为8.3%;阴性症状的组间疗效差异有统计学意义（P〈0.05）。除了轻微的一过性头痛和入睡困难,未见有其他严重不良反应。结论 TBS模式可改善精神分裂症患者的阴性症状。     

氯氮平治疗难治性抑郁症双盲对照观察

目的：探讨难治性抑郁症的治疗新途径。方法：把经两种抗抑郁剂先、后足量、足时治疗无效者（即难治性抑郁症）98例,随机分成两组,通过氯氮平或安慰剂合并抗抑郁剂分别治疗4周,进行双盲临床对照试验。结果：治疗2、4周末汉密尔顿抑郁量表（HAMD）分,氯氮平合并抗抑郁剂组（治疗组）明显低于治疗前,安慰剂合并抗抑郁剂组（对照组）降低无显著性。4周末HAMD减分率,治疗组明显优于对照组;总体评定量表（GAS）总有效率治疗组和对照组分别为68．8％、20．0％,以前者显著较高。副反应症状量表（TESS）两组无显著性差异。结论：氯氮平可能是治疗难治性抑郁症的有效药物之一。     

rTMS与MECT对难治性抑郁症疗效及认知功能影响的随机对照研究

目的 比较抗抑郁药联合重复经颅磁刺激(rTMS)或无抽搐电休克(MECT)治疗难治性抑郁症的疗效,并探讨两者对抑郁症患者认知功能的影响.方法 将40例难治性抑郁症患者随机分成rTMS治疗组和MECT治疗组,分别于治疗前、治疗1周、2周应用汉密尔顿抑郁量表(HAMD)和临床记忆量表评定临床疗效及认知功能改变,采用不良反应量表(TESS)、生命体征、体格检查、心电图、脑电图评价安全性.结果 两组患者HAMD总分、认知障碍因子分在治疗1周、2周差异无统计学意义(P>0.05);治疗2周后,rTMS组总分及各因子评分均较治疗前提高(P<0.05),MECT组指向记忆、无意义图形再认、人像特点回忆评分较治疗前明显下降(P<0.05);治疗后两组间比较,MECT组患者的临床记忆量表总分、指向记忆、图像自由回忆、人像特点回忆评分均显著低于rTMS组,差异有统计学意义(P<0.05).治疗中两组恶心、呕吐、头痛发生率的差异无统计学意义(P>0.05),MECT组主诉记忆力下降者比例高于rTMS组(P<0.05).结论 rTMS与MECT治疗难治性抑郁症疗效相当,rTMS对认知功能的改善作用优于MECT.     

奎硫平治疗难治性抑郁症的辅助作用

目的：探讨奎硫平治疗难治性抑郁症的增效作用及安全性。方法：58例难治性抑郁症患者分为研究组（抗抑郁药联合奎硫平治疗）和对照组（单用抗抑郁药治疗）各29例。观察6周。于治疗前及治疗1、2、4和6周采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评定疗效;以治疗中出现的症状量表（TESS）评定不良反应。结果：两组治疗后HAMD和HAMA评分均较治疗前有显著降分（P〈0.05或P〈0.001）;以研究组HAMD减分率自治疗1周起、HAMA减分率自治疗4周起均显著高于对照组（P〈0.01或P〈0.001）。两组治疗各周TESS评分差异均无统计学意义（P〉0.05）。结论：奎硫平治疗难治性抑郁症增效作用明显且安全。     

高频经颅磁刺激治疗抑郁症的临床疗效及对外周血白细胞介素-1、白细胞介素-10及肿瘤坏死因子-α水平的影响

目的:探讨高频经颅磁刺激治疗抑郁症的疗效及对患者外周血白细胞介素-1(IL-1)、IL-10及肿瘤坏死因子(TNF-α)水平的影响。方法:将60例住院抑郁症患者随机分为伪刺激组和重复经颅磁刺激(rTMS)组各30例。rTMS组接受高频(10 Hz)rTMS治疗，伪刺激组接受伪刺激治疗2周。采用汉密尔顿抑郁量表17项(HAMD-17)评估临床症状，在基线及治疗第2周时采用酶联免疫法测定血清IL-1、IL-10及TNF-α浓度。结果:伪刺激组和rTMS组HAMD评分在治疗2周均有降低，比较差异有统计学意义(P<0.05);治疗2周rTMS组有效率(76.67%)高于伪刺激组(46.67%),rTMS组IL-1及TNF-α降低程度与伪刺激组比较，差异有统计学意义(P<0.05)。结论:高频rTMS治疗抑郁症具有一定疗效，其发挥抗抑郁作用可能与炎症反应有关，值得临床推广使用。     

重复经颅磁刺激治疗对精神分裂症认知功能影响的对照研究

目的观察和评价重复经颅磁刺激（rTMS）治疗对精神分裂症患者认知功能的影响。方法收集精神分裂症患者，并随机分为rTMS真刺激组和rTMS伪刺激组，进行4周治疗。应用注意网络测验（ANT）和威斯康星卡片分类测验（WCST），在rTMS治疗前后评估患者的注意和执行功能。共23例患者完成治疗，rTMS真刺激组12例，rTMS伪刺激组11例。结果rTMS干预前后，两组的注意网络测验各项指标没有显示明显差异（P〉0．05）。与rTMS干预前相比，rTMS干预结束时，rTMS真刺激组的WCST测试总时间缩短（干预前536S±217S，干预后405S±174S；t=2．69，P〈0．05），错误思考时间缩短（干预前335S±148S，干预后233S±128S；t=3．19，P〈0．01）和选择错误率降低（干预前58．1％±14．8％，干预后51．6％4-15．3％；t=2．16，P：0．05）；rTMS伪刺激组WCST测试的正确思考时间也有缩短（P〈0．01）。结论重复经颅磁刺激rTMS治疗没有引起精神分裂症患者的认知功能损害。同时，有改善患者部分认知功能损害倾向，值得进一步研究。     

Effects of left frontal transcranial magnetic stimulation on depressed mood, cognition, and corticomotor threshold.

BACKGROUND: The pathophysiology of depression may include synaptic hypoactivity of left prefrontal cortex. Several groups of investigators have described improved mood associated with rapid transcranial magnetic stimulation (rTMS) but have not looked for possible cognitive side effects associated with left prefrontal magnetic stimulation. METHODS: We measured the effects of left prefrontal rTMS on mood, cognition, and motor evoked potential threshold in 10 patients with medication-resistant major depression. RESULTS: In a 2-week open trial of left prefrontal rTMS off antidepressant medications, scores on the Hamilton Rating Scale for Depression and the Beck Depression Inventory decreased by 41% and 40%, respectively. After resuming pre-rTMS antidepressant medication, improvement in mood was still significant at 1 and 3 months later. rTMS had no adverse effects on neuropsychological performance. rTMS treatments were associated with significant decreases in motor evoked potential threshold in the 9 of 10 patients who remained off psychotropic medications during the 2-week treatment period. CONCLUSIONS: These preliminary data suggest that left prefrontal rTMS is safe and improves mood in patients with medication-resistant major depression. Changes in motor evoked potential threshold suggest that prefrontal rTMS may alter brain activity at sites remote from the stimulation. Double-blind, sham-controlled studies are needed.     

Repetitive transcranial magnetic stimulation as add-on antidepressant treatment. The applicability of the method in a clinical setting

Recent research indicates that repetitive transcranial magnetic stimulation (rTMS) over the frontal cortex has an antidepressant effect. The aim of the present pilot study was to assess the antidepressant effect, side-effects and the applicability in daily clinical practice of left prefrontal high-frequency rTMS. Fifteen inpatients with major depression (ICD-10 and DSM-IV) were randomized to receive 15 days of real left prefrontal high-frequency rTMS (20 trains of 10 s, 60-s interval, 10 Hz, 90% of motor threshold) or sham rTMS as add on to conventional antidepressant treatment. Depressive symptoms and side-effects were evaluated blindly during the treatment period. Five out of eight patients receiving real rTMS suffered from local discomfort during treatment. Three of them dropped out and the project was closed for that reason. Real rTMS did not add efficacy to standard antidepressant medication. This pilot study did not confirm the antidepressant effect of left frontal high-frequency rTMS. Unwanted effects led to considerable patient drop-out and premature termination of the study. The result suggests that alternative treatment delivery technology should be considered.     

Repetitive transcranial magnetic stimulation as add-on antidepressant treatment. The applicability of the method in a clinical setting

Recent research indicates that repetitive transcranial magnetic stimulation (rTMS) over the frontal cortex has an antidepressant effect. The aim of the present pilot study was to assess the antidepressant effect, side-effects and the applicability in daily clinical practice of left prefrontal high-frequency rTMS. Fifteen inpatients with major depression (ICD-10 and DSM-IV) were randomized to receive 15 days of real left prefrontal high-frequency rTMS (20 trains of 10 s, 60-s interval, 10 Hz, 90% of motor threshold) or sham rTMS as add on to conventional antidepressant treatment. Depressive symptoms and side-effects were evaluated blindly during the treatment period. Five out of eight patients receiving real rTMS suffered from local discomfort during treatment. Three of them dropped out and the project was closed for that reason. Real rTMS did not add efficacy to standard antidepressant medication. This pilot study did not confirm the antidepressant effect of left frontal high-frequency rTMS.

Unwanted effects led to considerable patient drop-out and premature termination of the study. The result suggests that alternative treatment delivery technology should be considered.     

Cerebral blood flow in the ventromedial prefrontal cortex correlates with treatment response to low-frequency right prefrontal repetitive transcranial magnetic stimulation in the treatment of depression

Aims: Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression. Methods: We examined 26 depressed patients for the correlation between treatment response to rTMS and regional CBF in the frontal regions, by analyzing their brain scans with ^99mTc‐ethyl cysteinate dimer before rTMS treatment. CBF in 16 brain regions was estimated using fully automated region of interest analysis software. Two principal components were extracted from CBF in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. Results: Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions) and ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was not correlated with CBF in the dorsolateral prefrontal cortex, but it was correlated with CBF in the ventromedial prefrontal cortex. Conclusion: These findings suggest that CBF in the ventromedial prefrontal cortex may be a potential predictor of low‐frequency right prefrontal rTMS, and depressed patients with increased CBF in the ventromedial prefrontal cortex may show a better response.     

Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial

BACKGROUND: The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy. We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram. However, because a recent meta-analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients, we decided to make an interim analysis. METHOD: In patients with medication-resistant major depression we administered in a randomised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily. After the last rTMS, the patients were followed for another 9 weeks on 20 mg escitalopram daily. The antidepressant effect was measured by the HAM-D(6) as primary outcome scale. RESULTS: A total of 45 patients with complete data were randomised so that 23 patients received sham TMS and 22 patients received active, high-frequency rTMS over the left cortex. Over the 3 weeks, the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6) above 0.70, which indicates not only a statistically but also a clinically significant effect. The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study. Both the rTMS and escitalopram were well-tolerated. CONCLUSION: High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants.     

Antidepressant efficacy and cognitive effects of repetitive transcranial magnetic stimulation in vascular depression: an open trial

BACKGROUND: Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) were demonstrated by many controlled studies in major depression. Moreover, this promising and non invasive therapeutic tool seems to be better tolerated than electroconvulsive therapy.Vascular depression is a subtype of late-life depression, associated with cerebrovascular disease and means a poorer response to antidepressant treatment. We employed rTMS over the left prefrontal cortex in 11 patients with late-onset resistant vascular depression. The primary purpose of this two-week open study was to examine antidepressant efficacy of rTMS in vascular depression. The secondary aim was to evaluate cognitive effects of rTMS in our sample. METHODS: Clinical status, as measured with the Hamilton Depression Rating Scale (HDRS), and cognitive effects, as evaluated by neuropsychological tests, were assessed at baseline and after two weeks of rTMS. Brain measurements to obtain an index of prefrontal atrophy were performed at both the motor cortex and prefrontal cortex. RESULTS: Five out of 11 resistant patients with late-onset vascular depression were responders. They showed a clinically meaningful improvement in HDRS scores, with a decrease of 11, 4 points (p<0.01). Antidepressant response is correlated to the relative degree of prefrontal atrophy (p = 0.05). After two weeks, verbal fluency and visuospatial memory improved. No cognitive performance deteriorated except for verbal memory, as the delayed recall decreased significantly in the responders' group. CONCLUSIONS: Our preliminary observations prompt to perform a subsequent controlled study to examine if rTMS may constitute an alternative to electroconvulsive therapy.     

Combination rapid transcranial magnetic stimulation in treatment refractory depression

High frequency (>1 Hz) repetitive transcranial magnetic stimulation (rTMS) applied to the left prefrontal cortex and low frequency (≤1 Hz) rTMS applied to the right prefrontal cortex have shown antidepressant effects. However, the clinical significance of these effects has often been modest. It was hypothesized that a combination of these two techniques might act synergistically and result in more clinically relevant antidepressant effects. Sixty-two subjects with treatment-resistant major depression (an average of 8 failed medication trials) were randomized to receive combination right low frequency (1 Hz)/left high frequency (10 Hz) rTMS over the dorsolateral prefrontal cortex at 110% of the motor threshold vs sham rTMS. Subjects were treated for 2 weeks (10 weekday sessions) and received 1600 stimulations during each treatment session. Subjects receiving combination treatment were further randomized to receive different orders of treatment: right low frequency first (Slow Right) vs left high frequency first (Fast Left). There were no statistical differences in the active vs sham treatment arms in the primary outcome variable, the Hamilton Depression Rating Scale (HDRS). However compared with subjects in the Sham and Slow Right arms, there was a trend for subjects in the Fast Left arm to show improvement in the HDRS, the Beck Depression Inventory, and the Brief Psychotic Rating Scale with increased number of treatments. The Fast Left arm also showed significant improvement in both blinded clinician and self-ratings of global improvement. These differences were hypothesized to be due to the decreased number of failed medication trials for subjects in Fast Left arm. Neuropsychological performance was not significantly different between the sham and active rTMS arms. Future studies should increase the number of treatment sessions and focus on subjects with moderate treatment resistance.     

How coil-cortex distance relates to age, motor threshold, and antidepressant response to repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a tool with antidepressant potential that uses a coil placed on the scalp to produce a powerful magnetic field that directly stimulates only the outermost cortex. MRI scans were obtained in 29 depressed adults involved in an rTMS antidepressant clinical treatment. These scans were analyzed to investigate the effect of distance from coil to cortex on clinical parameters. Longer motor cortex distance, but not prefrontal distance, strongly correlated with increased motor threshold (P<0.01). Clinical antidepressant response did not correlate with either distance. The rTMS antidepressant responders, however, were significantly younger (t=-2.430, P<0.05), and there appears to be a maximum threshold of age and distance to prefrontal cortex for response.     

Changes in regional cerebral blood flow after repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in treatment-resistant depression

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex is effective in treatment-resistant depression, although its mechanism is still not completely elucidated. To clarify the neuroanatomical alteration of function elicited by rTMS, single photon emission computed tomography (SPECT) with (99m)Tc-ECD was performed on 12 male inpatients with treatment-resistant unipolar depression before and after high-frequency rTMS of the left dorsolateral prefrontal cortex. These results suggest that the manifestation of the antidepressant effect of high-frequency rTMS is associated with changes in the neuroanatomical function of the left dorsolateral prefrontal cortex as well as of the limbic-paralimbic region, including the ipsilateral subgenual cingulate, and the basal ganglia.     

Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients.

BACKGROUND: High (10-20 Hz) and low frequency (1-5 Hz) repetitive transcranial magnetic stimulation (rTMS) have been explored for possible therapeutic effects in the treatment of neuropsychiatric disorders. As part of a double-blind, placebo-controlled, crossover study evaluating the antidepressant effect of daily rTMS over the left prefrontal cortex, we evaluated changes in absolute regional cerebral blood flow (rCBF) after treatment with 1- and 20-Hz rTMS. Based on preclinical data, we postulated that high frequency rTMS would increase and low frequency rTMS would decrease flow in frontal and related subcortical circuits. METHODS: Ten medication-free, adult patients with major depression (eight unipolar and two bipolar) were serially imaged using (15)O water and positron emission tomography to measure rCBF. Each patient was scanned at baseline and 72 hours after 10 daily treatments with 20-Hz rTMS and 10 daily treatments with 1 Hz rTMS given in a randomized order. TMS was administered over the left prefrontal cortex at 100% of motor threshold (MT). Significant changes in rCBF from pretreatment baseline were determined by paired t test. RESULTS: Twenty-hertz rTMS over the left prefrontal cortex was associated only with increases in rCBF. Significant increases in rCBF across the group of all 10 patients were located in the prefrontal cortex (L > R), the cingulate gyrus (L > R), and the left amygdala, as well as bilateral insula, basal ganglia, uncus, hippocampus, parahippocampus, thalamus, and cerebellum. In contrast, 1-Hz rTMS was associated only with decreases in rCBF. Significant decreases in flow were noted in small areas of the right prefrontal cortex, left medial temporal cortex, left basal ganglia, and left amygdala. The changes in mood following the two rTMS frequencies were inversely related (r = -.78, p <.005, n = 10) such that individuals who improved with one frequency worsened with the other. CONCLUSIONS: These data indicate that 2 weeks of daily 20-Hz rTMS over the left prefrontal cortex at 100% MT induce persistent increases in rCBF in bilateral frontal, limbic, and paralimbic regions implicated in depression, whereas 1-Hz rTMS produces more circumscribed decreases (including in the left amygdala). These data demonstrate frequency-dependent, opposite effects of high and low frequency rTMS on local and distant regional brain activity that may have important implications for clinical therapeutics in various neuropsychiatric disorders.