Bilateral Repetitive Transcranial Magnetic Stimulation Research Articles

Commentary on: "effects of motor imagery-based neurofeedback training after bilateral repetitive transcranial magnetic stimulation on post-stroke upper limb motor function: an exploratory crossover clinical trial".

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Clinical and neurophysiological effects of bilateral repetitive transcranial magnetic stimulation and EEG-guided neurofeedback in Parkinson’s disease: a randomized, four-arm controlled trial

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson’s disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD.MethodsA randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models.ResultsForty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1–3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found.ConclusionsThe combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels.Trial registrationNCT04017481.

Cognitive Profiles in Treatment-Resistant Late-Life Depression and Their Impact on Treatment Outcomes

BackgroundLate-life depression (LLD) is associated with cognitive impairment, but substantial heterogeneity exists among patients. Data on the extent of cognitive impairments are inconclusive, particularly in patients with treatment-resistant depression (TRD). We investigated the cognitive profiles of patients with treatment-resistant versus nonresistant LLD and aimed to identify distinct cognitive subgroups. We also examined whether cognitive subgroups responded differentially to treatment with bilateral repetitive transcranial magnetic stimulation (rTMS). MethodsA total of 165 patients with LLD were divided into treatment-resistant and nonresistant groups and compared with healthy control participants on measures of executive function, information processing speed, verbal learning, and memory. Cluster analysis identified subgroups based on cognitive scores. Demographic and clinical variables, as well as outcomes with bilateral rTMS, were compared between cognitive subgroups. ResultsPatients with LLD, particularly TRD, exhibited significantly worse cognitive performance than healthy controls. A 3-cluster solution was found, including cognitively intact (n = 89), cognitively diminished (n = 29), and impaired memory (n = 47) subgroups. Both the cognitively diminished and impaired memory subgroups had more anxiety symptoms and a higher proportion of patients with TRD than the cognitively intact group, although the latter difference did not survive multiple comparison correction. No significant differences were observed in outcomes to rTMS treatment. ConclusionsPatients with LLD exhibited impairments across cognitive domains, which were more pronounced in TRD. Three cognitive subgroups responded similarly to rTMS treatment, indicating its effectiveness across cognitive profiles, especially when medications are not tolerated. Future research should examine the relationships among cognitive subgroups, cognitive decline, and neurodegeneration.

Acute treatment of bilateral rTMS combined with antidepressants on the plasma fatty acids for major depressive episodes

Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baselinephase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.

Efficacy of insula deep repetitive transcranial magnetic stimulation combined with varenicline for smoking cessation: A randomized, double-blind, sham controlled trial

BackgroundCurrent smoking cessation treatments are limited in terms of efficacy, particularly with regards to long term abstinence. There is a large amount of evidence implicating the insula in nicotine addiction. ObjectiveTo examine the efficacy of bilateral repetitive transcranial magnetic stimulation (rTMS) directed to the insular cortex with the H11 coil, relative to sham stimulation, on smoking abstinence and smoking outcomes in smokers who are receiving standard varenicline treatment. MethodsThis randomized, double-blind, sham controlled trial recruited 42 participants who were randomized to receive either active (n = 24) or sham (n = 18) high frequency rTMS directed to the insula (4 weeks), while receiving varenicline treatment (12 weeks). The primary outcome was 7-day point prevalence abstinence at the end of 12 weeks. ResultsSmokers in the active group had significantly higher abstinence rates than those in the sham group (82.4% vs. 30.7%, p = 0.013) at the end of treatment (Week 12). Secondary outcome measures of abstinence rate at the end of rTMS treatment (Week 4), abstinence rate at 6 months, and smoking outcomes (e.g., craving, withdrawal) showed no significant differences between groups. No differences were found in adverse events reported between the groups. ConclusionThis study provides evidence of the potential benefit of having a combined treatment for smoking cessation using insula rTMS with the H11 coil and varenicline. Maintenance rTMS sessions and continuation of varenicline for those in abstinence may induce longer-term effects and should be considered in future studies.

Effect of prior pharmacotherapy on remission with sequential bilateral theta-burst versus standard bilateral repetitive transcranial magnetic stimulation in treatment-resistant late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is used for treatment of late-life depression. In the FOUR-D study, sequential bilateral theta-burst stimulation (TBS) had comparable remission rates to standard bilateral rTMS. Data were analysed from the FOUR-D trial to compare remission rates between two types of rTMS based on the number and class of prior medication trials. The remission rate was higher in participants with ≤1 previous trial (43.9%) than in participants with 2 previous trials (26.5%) or ≥3 previous trials (24.6%; χ² = 6.36, d.f. = 2, P = 0.04). Utilising rTMS earlier in late-life depression may lead to better outcomes.

Tolerability of transcranial magnetic stimulation language mapping in children

ObjectiveTranscranial Magnetic Stimulation (TMS) has emerged as a viable non-invasive method for mapping language networks. Little is known about the tolerability of transcranial magnetic stimulation language mapping in children. MethodsChildren aged 5–18 years underwent bilateral language mapping using repetitive transcranial magnetic stimulation (rTMS) to target 33 sites/hemisphere. Stimulation was delivered at 5 Hz, in 1–2 second bursts, during visual naming and auditory verb generation. Pain unpleasantness and pain intensity were assessed using an unpleasantness visual analog scale (VAS). Results49 participants tolerated motor mapping and had repetitive transcranial magnetic stimulation. 35/49 (71%) completed visual naming and 26/49 (53%) completed both visual naming and verb generation. Mean electrical field per participant was 115 V/m. Young age and lower language ability were associated with lower completion. Visual analogue scale scores were significantly higher (6.1 vs. 2.8) in participants who withdrew early compared to those who completed at least visual naming. ConclusionsPain measured by VAS was a major contributor to early withdrawal. However, a complete bilateral map was obtained with one paradigm in 71% of participants. Future studies designed to reduce pain during repetitive transcranial magnetic stimulation over language cortex will boost viability. SignificanceThis study represents the first attempt to characterize tolerability of bilateral repetitive transcranial magnetic stimulation language mapping in healthy children.

Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression

Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes. To establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD. In this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials. Participants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS. The primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed. A total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P = .14; χ2 = 2.2). In older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD. ClinicalTrials.gov Identifier: NCT02998580.

Bilateral repetitive transcranial magnetic stimulation ameliorated sleep disorder and hypothalamic-pituitary-adrenal axis dysfunction in subjects with major depression.

ObjectiveIn this study, we sought to explore the effectiveness of bilateral repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) on depressive symptoms and dysfunction of hypothalamic–pituitary–adrenal (HPA) axis in patients with major depressive disorder (MDD).Materials and methodsOne hundred and thirty-six adults with MDD were administrated drugs combined with 3 weeks of active rTMS (n = 68) or sham (n = 68) treatment. The 17-item Hamilton Depression Rating Scale for Depression (HAMD-17) was to elevate depression severity at baseline and weeks 4. To test the influence of rTMS on the HPA axis, plasma adrenocorticotropic hormone (ACTH) and serum cortisol (COR) were detected in pre- and post-treatment.ResultsNo statistical significance was found for the baseline of sociodemographic, characteristics of depression, and psychopharmaceutical dosages between sham and rTMS groups (p > 0.05). There was a significant difference in the HAMD-17 total score between the two groups at end of 4 weeks after treatment (p < 0.05). Compared to the sham group, the rTMS group demonstrated a more significant score reduction of HAMD-17 and sleep disorder factor (HAMD-SLD) including sleep onset latency, middle awakening, and early awakening items at end of 4-week after treatment (p < 0.05). Furthermore, total score reduction of HAMD-17 was correlated with a decrease in plasma ACTH, not in COR, by rTMS stimulation (p < 0.05).ConclusionBilateral rTMS for 3 weeks palliated depression via improvement of sleep disorder, and plasma ACTH is a predictor for the efficacy of rTMS, especially in male patients with MDD.

Effect of Ipsilateral, Contralateral or Bilateral Repetitive Transcranial Magnetic Stimulation in Patients with Lateralized Tinnitus: A Placebo-Controlled Randomized Study.

The relative benefit of ipsilateral, contralateral, and bilateral repetitive transcranial magnetic stimulation (rTMS) for tinnitus treatment remains unclear, especially for patients with lateralized tinnitus. In this study, we compared outcomes after 10 sessions of 1-Hz rTMS at 110% of resting motor threshold over a two-week period. In total, 104 right-handed patients with lateralized subjective tinnitus were randomly divided into four groups according to rTMS treatment: Left (n = 29), Right (n = 23), Bilateral (n = 30), and Sham stimulation (n = 22). Outcomes included estimates of tinnitus severity, psychological state, and psychoacoustic measures. Patients with left- or right-sided tinnitus were similarly distributed across treatment groups. There were no significant changes in outcome measures for the Right or Sham treatment groups. For the Left and Bilateral groups, tinnitus severity was significantly lower after treatment (p < 0.05). The reduction in tinnitus severity was largest for ipsilateral treatment in the Left group. The overall response rate was 56.1% for the Left group, 46.7% for the Bilateral group, 8.3% for the Right group, and 8.3% for the Sham group. For the Left and Bilateral groups, the response rate was larger for patients with left- than right-sided tinnitus. Changes in tinnitus severity were best predicted by changes in anxiety, depression, and the loudness of the tinnitus. The results suggests that rTMS on the left temporoparietal cortex is more effective for patients with left-sided than with right-sided tinnitus.

Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study

Patients with schizophrenia have a high prevalence of cigarette smoking and respond poorly to conventional treatments, highlighting the need for new therapies. We conducted a mechanistic, proof-of-concept study using bilateral deep repetitive transcranial magnetic stimulation (dTMS) of insular and prefrontal cortices at high frequency, using the specialized H4 coil. Feasibility of dTMS was tested for disruption of tobacco self-administration, insula target engagement, and insula circuit modulation, all of which were a priori outcomes of interest. Twenty patients completed the study, consisting of weekday dTMS sessions (randomization to active dTMS or sham; double-blind; 10 patients per group), a laboratory tobacco self-administration paradigm (pre/post assessments), and multimodal imaging (three MRI total sessions). Results showed that participants assigned to active dTMS were slower to initiate smoking their first cigarette compared with sham, consistent with smoking disruption. The imaging analyses did not reveal significant Time × Group interactions, but effects were in the anticipated directions. In arterial spin labeling analyses testing for target engagement, an overall decrease in insula blood flow, measured during a post-treatment MRI versus baseline, was numerically more pronounced in the active dTMS group than sham. In fMRI analyses, resting-state connectivity between the insula and default mode network showed a numerically greater change from baseline in the active dTMS group than sham, consistent with a functional change to insula circuits. Exploratory analyses further suggested a therapeutic effect of dTMS on symptoms of psychosis. These initial observations pave the way for future confirmatory studies of dTMS in smoking patients with schizophrenia.

Assessment of multiple salivary biomarkers during repetitive transcranial magnetic stimulation (rTMS) treatment for major depression

Steroid hormones may serve as potential biomarkers of treatment response for major depressive disorder (MDD). Here, we assessed salivary levels of cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S), as well as α-amylase activity, across 30 sessions of bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in MDD patients. While rTMS significantly improved symptoms as measured by three different symptom scales, salivary biomarker levels and their ratios showed no significant changes across sessions. These results do not support the routine clinical use of these biomarkers as reliable indicators of treatment outcome during rTMS administration for MDD.

Bilateral Repetitive Transcranial Magnetic Stimulation With the H-Coil in Parkinson's Disease: A Randomized, Sham-Controlled Study.

Background: Pilot open-label application of high-frequency repetitive transcranial magnetic stimulation (rTMS) with H-coil in Parkinson's Disease (PD) have shown promising results.Objective: To evaluate safety and efficacy of high-frequency rTMS with H-coil in PD in a double-blind, placebo-controlled, randomized study.Methods: Sixty patients with PD were randomized into 3 groups: M1-PFC (real stimulation on primary motor-M1 and pre-frontal cortices-PFC), M1 (real rTMS on M1, sham on PFC), Sham (apparent stimulation). Primary outcome was baseline-normalized percent improvement in UPDRS part III OFF-therapy at the end of treatment (12 rTMS sessions, 4 weeks). Secondary outcomes were improvement in UPDRS part III sub-scores, timed tests, and neuropsychological tests. Statistical analysis compared improvement following real and sham stimulation at the end of the protocol using either a t-test or a Mann-Whitney test.Results: All patients tolerated the treatment and concluded the study. One patient from M1-PFC group was excluded from the analysis due to newly discovered uncontrolled diabetes mellitus. No serious adverse effect was recorded. At the end of treatment, patients receiving real rTMS (M1-PFC and M1 combined) showed significantly greater improvement compared to sham in UPDRS part III total score (p = 0.007), tremor subscore (p = 0.011), and lateralized sub-scores (p = 0.042 for the more affected side; p = 0.012 for the less affected side). No significant differences have been oserved in safety and efficacy outcomes between the two real rTMS groups. Notably, mild, not-distressing and transient dyskinesias occurred in 3 patients after real rTMS in OFF state.Conclusions: The present findings suggest that high-frequency rTMS with H-coil is a safe and potentially effective procedure and prompt larger studies for validation as add-on treatment in PD.

Long-Term, Bilateral Repetitive Transcranial Magnetic Stimulation in a Patient with Locked-In Syndrome

Long-Term, Bilateral Repetitive Transcranial Magnetic Stimulation in a Patient with Locked-In Syndrome

Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades

Approximately 35% of people with depression do not respond to 2 courses of antidepressant medications of adequate dosage, and treatment-resistant depression (TRD) is still a major clinical concern with a great impact on patients, their families, society and the health system. The present meta-analysis evaluates antidepressant efficacy of unilateral and bilateral repetitive transcranial magnetic stimulation (rTMS) in patients with unipolar TRD. We searched for randomized controlled trials that compared rTMS with sham treatment and were published by Apr. 3, 2017. The primary outcome was improvement in depression scores measured using the Hamilton Rating Scale for Depression. The secondary outcomes were remission and response rates. Two independent review authors screened the studies and extracted the data. Twenty-three studies met the inclusion criteria. Meta-analysis of the depression scores showed a weighted mean difference (WMD) of 3.36 (95% confidence interval [CI] 1.85–4.88) between unilateral rTMS and sham treatment. Stratified data showed that the effect was relatively higher when rTMS was used as an add-on to antidepressant medications (WMD 3.64, 95% CI 1.52–5.76) than when it was used as a stand-alone treatment (WMD 2.47, 95% CI 0.90–4.05). The WMD between bilateral rTMS and sham was 2.67 (95% CI 0.83–4.51), and all studies that contributed to this outcome used rTMS while participants were taking antidepressant medications. The pooled remission and response rates for unilateral rTMS versus sham treatment were 16.0% and 25.1% for rTMS and 5.7% and 11.0% for sham treatment, respectively. The pooled remission and response rates for bilateral rTMS versus sham treatment were 16.6% and 25.4% for rTMS and 2.0% and 6.8% for sham treatment, respectively. This study suggests that rTMS has moderate antidepressant effects and appears to be promising in the short-term treatment of patients with unipolar TRD.

Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant late-life depression.

The management of late-life depression is challenged by high rates of treatment-resistance and adverse effects, along with medical comorbidities and polypharmacy. Together with the limited data on managing treatment-resistant depression in older adults, there is a need for investigating the efficacy of nonpharmacological treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is one modality that may better serve this patient population. The present study examines data from two previous clinical trials (NCT00305045 and NCT01515215) to explore the efficacy of bilateral and unilateral high-frequency left-sided (HFL) rTMS in older adults suffering from treatment-resistant depression. A total of 43 adults aged 60 or older with a current major depressive episode were randomized to bilateral sequential, unilateral HFL, or sham. Bilateral sequential stimulation involved low-frequency (1 Hz) right dorsolateral prefrontal cortex (DLPFC) stimulation followed immediately by high-frequency (10 Hz) left DLPFC. The unilateral condition was HFL stimulation alone, and the placebo condition was either HFL or sequential bilateral form of sham. The primary outcome was remission of depression. Participants receiving bilateral rTMS experienced greater remission rates (40%) compared with unilateral (0%) or sham (0%) groups. Response to rTMS in the Hamilton Depression Rating Scale scores similarly favored the efficacy of bilateral rTMS. This study suggests that sequential bilateral treatment may be an optimal form of rTMS when used for treatment-resistant depression in older adults. Further large-scale comparative effectiveness trials of bilateral rTMS in this population are warranted.

Bilateral Repetitive Transcranial Magnetic Stimulation in Older Adults with Depression

Depression is the most common, treatable, mental disorder in late life, making it a major public health concern: 2 to 4 % of persons over the age of 65 suffer from major depression. Current pharmacological treatments for LLD, however, provide modest efficacy. Rates of treatment resistance in randomized controlled trials (RCT) in LLD range from 55-81% using first line antidepressants. The failure of first line treatment to induce remission in patients leads to impaired psychosocial function and diminished quality of life. Depression in older adults, and non-response to antidepressants, is associated with low connectivity in the cognitive control network. Cognition, in particular executive function and processing speed, are often impaired in LLD. It is an important predictor of acute antidepressant treatment outcome. In a 2010 report from the National Institutes of Health (NIH), depression was identified as one of six potentially modifiable risks for cognitive decline, AD, or both. Successful interventions targeting depression could reduce the prevalence of AD by up to 15% in North America, making depression the second most promising target for prevention studies after physical inactivity. Data from three randomized sham controlled trials that have included older adults show converging evidence for the efficacy of bilateral repetitive transcranial magnetic stimulation in this population. Emerging data suggests that intermittent theta burst stimulation (TBS) is similar in effectiveness to high frequency rTMS. An ongoing study is exploring the effectiveness of bilateral (low frequency right then high frequency left) dorsolateral prefontal rTMS compared to continuous TBS right and intermittent TBS left in older adults with depression while also examining the effects on cognition. The design and interim results of this trial will be presented.

The Effectiveness of Bilateral Repetitive Transcranial Magnetic Stimulation in Anhedonia among Patient with Major Depressive Disorder: A pilot study

High-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) is now commonly used treatment for patients with depression. However, there are several other forms of rTMS (low-frequency right-sided and sequential bilateral rTMS) which have also been shown to be effective. No information has been systematically gathered on the likelihood of response to alternative forms of rTMS in patients who do not improve after an initial course of left-sided treatment.To evaluate whether there are differences in antidepressant response between switching to either low-frequency right sided or sequential bilateral stimulation or continuing high-frequency left-sided TMS following non-response to an initial course of high-frequency left-sided rTMS.113 rTMS naïve patients were provided with an initial three-week course of high-frequency left-sided rTMS. Non-responders were then randomised to receive another three weeks of left-sided treatment (n = 21), right-sided low frequency stimulation (n = 18) or sequential bilateral rTMS (n = 20).Although there was an overall improvement in depressive symptoms in the randomised phase of the study, no significant differences in response was seen between the three treatment groups on Montgomery Asberg Depression Rating Scale or Hamilton Depression Rating Scale scores.The main limitation of the study was the duration of treatment provided in both the lead in and random treatment phases.This study does not provide evidence for differences in response to different forms of rTMS in initial non-responders to left-sided stimulation. However, further studies with longer periods of treatment and a larger sample size are required to definitively establish or exclude between group differences in rTMS response in initial non-responders to treatment.

Bilateral Transcranial Magnetic Stimulation on DLPFC Changes Resting State Networks and Cognitive Function in Patients With Bipolar Depression.

Introduction: Bipolar patients have abnormalities in cognitive functions and emotional processing. Two resting state networks (RSNs), the default mode network (DMN) and the sensorimotor network (SMN), play a decisive role in these two functions. Dorsolateral prefrontal cortex (DLPFC) is one of the main areas in the central executive network (CEN), which is linked to the activities of each of the two networks. Studies have found DLPFC abnormalities in both hemispheres of patients with bipolar depression. We hypothesized that the bilateral repetitive transcranial magnetic stimulation (rTMS) of DLPFC would produce changes in the activity of both the SMN and DMN as well as relevant cognitive function in patients with bipolar depression that responded to treatment.Methods: 20 patients with bipolar depression underwent 10 sessions of 1 Hz rTMS on right DLPFC with subsequent 10 Hz rTMS on left DLPFC. Changes in electroencephalography resting networks between pre and post rTMS were evaluated utilizing low-resolution electromagnetic tomography (eLORETA). Depression symptom was assessed using the Beck Depression Inventory (BDI-II) and cognitive function was assessed by Verbal Fluency Test (VFT), Rey Auditory Verbal Learning Test (RAVLT), Stroop Test, and Wisconsin Card Sorting Test (WCST).Results: Responders to rTMS showed significantly lower DMN activity at baseline and a significant decrease in SMN connectivity after treatment. Non-responders did not significantly differ from the control group at the baseline and they showed higher activity in the SMN, visual network, and visual perception network compared to control group following treatment. Bilateral rTMS resulted in significant changes in the executive functions, verbal memory, and depression symptoms. No significant changes were observed in selective attention and verbal fluency.Conclusion: Bilateral stimulation of DLPFC, as the main node of CEN, results in changes in the activity of the SMN and consequently improves verbal memory and executive functions in patients with bipolar depression.

Bilateral Repetitive Transcranial Magnetic Stimulation Decreases Suicidal Ideation in Depression.

The purpose of this study was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on suicidal ideation in patients with treatment-resistant major depression (TRD) (patients who failed to clinically respond to at least 2 medication trials). We pooled data from 2 published prospective randomized controlled trials of rTMS applied to the dorsolateral prefrontal cortex in patients with TRD. We compared the effect of bilateral, left unilateral, and sham rTMS on suicidal ideation as measured by the suicide item of the 17-item Hamilton Depression Rating Scale (HDRS) (N = 156). Suicidal ideation resolved in 40.4%, 26.8%, and 18.8% of participants randomized to bilateral, left unilateral, and sham rTMS, respectively. The difference between bilateral and sham was significant (OR = 3.03; 95% CI, 1.19-7.71; P = .02), unlike the difference between left unilateral and sham (OR = 1.59; 95% CI, 0.61-4.12; P = .33). There was a modest correlation between change in suicidal ideation and change in depression severity (Pearson r = 0.38; P < .001) and no difference in change of HDRS-16 score between suicide remitters and nonremitters (P = .32). Bilateral rTMS was superior to sham rTMS in reducing suicidal ideation in patients with TRD. Only a small portion of the reduction in suicidal ideation was attributable to the reduction in depressive symptoms. These data suggest that suicidal ideation could be a specific target symptom construct for rTMS. ClinicalTrials.gov identifiers: NCT01515215 and NCT00305045.