***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Multiple groups have reported on the use of repetitive transcranial magnetic stimulation ( rTMS ) in treatment-resistant major depression . The purpose of this study is to assess the efficacy of rTMS in unmedicated , treatment-resistant patients who meet criteria for major depression . METHODS Depressed subjects , who had failed to respond to a median of four treatment trials , were assigned in a r and omized double-blind manner to receive either active ( n = 10 ; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals ; delivered at 80 % motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex ) or sham ( n = 10 ; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp ) rTMS . These sequences were applied during 10 consecutive weekdays . Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained . RESULTS The group mean 25-item Hamilton Depression Rating Scale ( HDRS ) score was 37.2 ( + /- 2.0 SEM ) points . Adjusted mean decreases in HDRS scores were 14.0 ( + /- 3.7 ) and 0.2 ( + /- 4.1 ) points for the active and control groups , respectively ( p < .05 ) . One of 10 subjects receiving active treatment demonstrated a robust response ( i.e. , HDRS decreased from 47 to 7 points ) ; three other patients demonstrated 40 - 45 % decreases in HDRS scores . No patients receiving sham treatment demonstrated partial or full responses . CONCLUSIONS A 2-week course of active rTMS result ed in statistically significant but clinical ly modest reductions of depressive symptoms , as compared to sham rTMS in a population characterized by treatment resistance Major depressive disorder ( MDD ) is a prevalent and disabling condition , and many patients do not respond to available treatments . Deep transcranial magnetic stimulation ( dTMS ) is a new technology allowing non-surgical stimulation of relatively deep brain areas . This is the first double-blind r and omized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD . We recruited 212 MDD out patients , aged 22 - 68 years , who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode . They were r and omly assigned to monotherapy with active or sham dTMS . Twenty sessions of dTMS ( 18 Hz over the prefrontal cortex ) were applied during 4 weeks acutely , and then biweekly for 12 weeks . Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale ( HDRS-21 ) score and response/remission rates at week 5 , respectively . dTMS induced a 6.39 point improvement in HDRS-21 scores , while a 3.28 point improvement was observed in the sham group ( p=0.008 ) , result ing in a 0.76 effect size . Response and remission rates were higher in the dTMS than in the sham group ( response : 38.4 vs. 21.4 % , p=0.013 ; remission : 32.6 vs. 14.6 % , p=0.005 ) . These differences between active and sham treatment were stable during the 12-week maintenance phase . dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred . These results suggest that dTMS constitutes a novel intervention in MDD , which is efficacious and safe in patients not responding to antidepressant medications , and whose effect remains stable over 3 months of maintenance treatment Repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression . However , the exact neurophysiological basis of these effects needs further clarification . Therefore , we studied the impact of ten daily sessions of left , dorsolateral prefrontal rTMS on motor cortical excitability , as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients . As compared to the non-responders , responders ( 33 % ) showed changes in parameters pointing towards a reduced cortical excitability . These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral , prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder . Furthermore , measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Objectives . Intensified repetitive transcranial magnetic stimulation ( rTMS ) applied to the left dorsolateral prefrontal cortex ( DLPFC ) may result in fast clinical responses in treatment resistant depression ( TRD ) . In these kinds of patients , subgenual anterior cingulate cortex ( sgACC ) functional connectivity ( FC ) seems to be consistently disturbed . So far , no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available . Methods . Twenty unipolar TRD patients , all at least stage III treatment resistant , were recruited in a r and omized sham-controlled crossover high-frequency (HF)-rTMS treatment study . Resting-state ( rs )  functional MRI scans were collected at baseline and at the end of treatment . Results . HF-rTMS responders showed significantly stronger resting-state functional connectivity ( rsFC ) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex . After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex ( pgPFC ) . No effects on sgACC rsFC were observed in non-responders . Conclusions . Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome . Accelerated HF-rTMS treatment design s have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients BACKGROUND Electroconvulsive therapy ( ECT ) is an effective alternative for pharmacotherapy in treatment-resistant depressive patients , but the side effects limit its use . Transcranial magnetic stimulation ( TMS ) has been proposed as a refined alternative , but most studies do not indicate that TMS is as effective as ECT for severe depression . OBJECTIVE We propose that the limited effectiveness of st and ard TMS resides in its superficial effect on the cortex , although much of the pathophysiology of depression is associated with deeper and larger brain regions implicated in the reward system . Herein , we tested the effectiveness and safety of a novel TMS coil , the " H-coil , " which enables direct stimulation of deeper brain regions , at the expense of focality . METHODS We have studied the antidepressant and cognitive effects induced by 4 weeks of high-frequency ( 20 Hz ) repeated deep TMS ( DTMS ) over the prefrontal cortex ( PFC ) of 65 medication-free depressive patients , who have failed to benefit from prior medications . Patients were r and omly assigned to various treatment configurations , differing in stimulation intensity and laterality . Effects were assessed by the 24-item Hamilton depression rating scale ( HDRS-24 ) and several secondary outcome measures . RESULTS A significant improvement in HDRS scores was found when high , but not low , stimulation intensity was used . Several cognitive improvements were evident , and no treatment-related serious adverse events were observed . CONCLUSIONS DTMS over the PFC was found safe and effective in alleviating depression . The results accentuate the significance of deep , high-intensity stimulation over low , and serve as the first study to indicate the potential of DTMS in psychiatric and neurologic disorders BACKGROUND We tested whether transcranial magnetic stimulation ( TMS ) over the left dorsolateral prefrontal cortex ( DLPFC ) is effective and safe in the acute treatment of major depression . METHODS In a double-blind , multisite study , 301 medication-free patients with major depression who had not benefited from prior treatment were r and omized to active  ( n = 155 ) or  sham TMS  ( n = 146 ) conditions . Sessions were conducted five times per week with TMS at 10 pulses/sec , 120 % of motor threshold , 3000 pulses/session , for 4 - 6 weeks . Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale ( HAMD ) and response and remission rates with the MADRS and HAMD . RESULTS Active TMS was significantly superior to sham TMS on the MADRS at week 4 ( with a post hoc correction for ine quality in symptom severity between groups at baseline ) , as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6 . Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6 . Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales ( but not the HAMD17 scale ) . Active TMS was well tolerated with a low dropout rate for adverse events ( 4.5 % ) that were generally mild and limited to transient scalp discomfort or pain . CONCLUSIONS Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported . It offers clinicians a novel alternative for the treatment of this disorder OBJECTIVE Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity . The authors sought to confirm this finding by using a double-blind crossover design . METHOD Twelve depressed adults received in r and om order 2 weeks of  active treatment ( repetitive transcranial magnetic stimulation , 20 Hz at 80 % motor threshold ) and 2 weeks of sham treatment . RESULTS Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment . During the active-treatment phase , Hamilton depression scale scores decreased 5 points , while during sham treatment the scores increased or worsened by 3 points . No adverse effects were noted . CONCLUSIONS These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters . Further controlled studies are indicated to explore optimal stimulation characteristics and location , potential clinical applications , and possible mechanisms of action It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 Background The aim of the current study was to investigate the cognitive correlates of repetitive transcranial magnetic stimulation ( rTMS ) in 10 treatment-resistant depression patients . Methods Patients received forty 20-min sessions of fast-frequency ( 10 Hz ) rTMS of the left dorsolateral prefrontal cortex ( DLPFC ) over 20 days . Concept-shift ability ( accuracy and duration of performance ) was assessed daily with a Modified Concept-Shifting Task ( mCST ) in patients and in eight healthy volunteers .  General cognitive functioning test ( Repeatable Battery for the Assessment of Neuropsychological Status ; RBANS ) , Beck Depression Inventory ( BDI ) and Hamilton Depression Rating Scale ( HAM-D ) were applied before the first and after the last rTMS . Results Compared to before rTMS on the first 10 days , the patients performed the mCST significantly more accurately after rTMS on the last 10 days ( p < .001 , partial eta squared=.78 ) while the same comparison in healthy volunteers was not statistically significant ( p = .256 , partial eta squared=.18 ) . A significant improvement in immediate memory on RBANS and reduction in BDI and HAM-D scores were also observed after the last compared to before the first rTMS . Conclusion The rTMS is associated with an improvement in selective cognitive functions that is not explained by practice effects on tasks administered repeatedly . Trial registration Name : " Repetitive Transcranial Magnetic Stimulation ( rTMS ) in the treatment of depression , assessed with HAM-D over a four week period."URL : www.actr.org.au Registration number : R and omized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation ( TMS ) ; however , there is individual variability in the magnitude of response . Examination of response predictors has been hampered by method ological limitations such as small sample sizes and single-site study design s. Data from a multisite sham-controlled trial of the antidepressant efficacy 
    Output:
    
Reduction in depression severity was greater in studies with younger patients using either coil .
The comparison between coils showed a larger reduction in depression severity in H1-coil vs. F8-coil studies ( independent of the study design or the concurrent pharmacotherapy ) and a trend towards higher remission rates in F8-coil vs. H1-coils studies .
Conclusion When matched on frequency , the higher-intensity and less focal stimulation with the H1-coil reduces depression more than the lower-intensity and more focal stimulation with the F8-coil .