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Motor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to either low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of left dPMC, rTMS of left M1, or sham rTMS. rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess potential stimulation-induced changes in corticospinal excitability (CSE). Participants were retested on motor sequence performance after eight hours to assess consolidation. While rTMS of dPMC significantly increased CSE and rTMS of M1 significantly decreased CSE, no CSE modulation was induced by sham rTMS. However, all groups demonstrated similar significant offline learning indicating that consolidation was not modulated by the post-training low-frequency rTMS intervention despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by low-frequency rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE., (© 2021. The Author(s).)

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute treatment, there are no published studies of continuation MST for the prevention of relapse., Methods: Patients with TRD with a DSM-IV diagnosis of major depressive disorder or bipolar disorder who met response criteria after acute MST were offered continuation MST in a prospective, open-label trial between February 2012 and June 2019. They received 12 continuation MST sessions with decreasing frequency over the course of 6 months, with additional booster sessions if their depression symptoms started to worsen. The primary outcome was relapse of depression or psychiatric hospitalization. Secondary outcomes included relapse of suicidal ideation and neurocognitive outcomes., Results: Thirty participants completing at least one assessment during continuation MST were included in the analysis; 10 (33.3%) relapsed, with no significant differences in survival distributions between unipolar and bipolar groups (χ 2  = 0.3, P  = .58). Mean (SD) survival time was 18.6 (1.6) weeks. All 17 participants who achieved resolution of baseline suicidality after acute MST remained free of suicidality during the continuation phase. Except for improvement in verbal fluency, neurocognitive test scores did not change during continuation MST., Conclusions: During 6 months of continuation MST, two-thirds of participants sustained improvements in depressive symptoms without any adverse cognitive effects. Future studies of continuation MST are warranted, particularly in comparison to ECT., Trial Registration: ClinicalTrials.gov identifier: NCT01596608., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Background: Robot-assisted therapy and noninvasive brain stimulation (NIBS) are promising strategies for stroke rehabilitation., Objective: This systematic review and meta-analysis aims to evaluate the evidence of NIBS as an add-on intervention to robotic therapy in order to improve outcomes of upper-limb motor impairment or activity in individuals with stroke., Methods: This study was performed according to the PRISMA Protocol and was previously registered on the PROSPERO Platform (CRD42017054563). Seven databases and gray literature were systematically searched by 2 reviewers, and 1176 registers were accessed. Eight randomized clinical trials with upper-limb body structure/function or activity limitation outcome measures were included. Subgroup analyses were performed according to phase poststroke, device characteristics (ie, arm support, joints involved, unimanual or bimanual training), NIBS paradigm, timing of stimulation, and number of sessions. The Grade-Pro Software was used to assess quality of the evidence., Results: A nonsignificant homogeneous summary effect size was found both for body structure function domain (mean difference [MD] = 0.15; 95% CI = -3.10 to 3.40; P = 0.93; I 2 = 0%) and activity limitation domain (standard MD = 0.03; 95% CI = -0.28 to 0.33; P = 0.87; I 2 = 0%)., Conclusions: According to this systematic review and meta-analysis, at the moment, there are not enough data about the benefits of NIBS as an add-on intervention to robot-assisted therapy on upper-limb motor function or activity in individuals with stroke.

Objective: The aim of the study was to examine the effectiveness of noninvasive brain stimulation on neuropathic pain in individuals with spinal cord injury., Methods: A meta-analysis on pain intensity, depression, and anxiety levels was conducted to evaluate the effect of noninvasive brain stimulation on neuropathic pain in individuals with spinal cord injury. The authors searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), Embase (OvidSP), PsycINFO (OvidSP), and Physiotherapy Evidence Database (PEDro). Randomized controlled trials comparing noninvasive brain stimulation with sham stimulation were included., Results: Eleven studies were selected. The pooled analysis demonstrated no significant effect of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, or cranial electrotherapy stimulation on neuropathic pain reduction after spinal cord injury. In addition, noninvasive brain stimulation showed no beneficial effect over sham stimulation on the improvement of depression, while it yielded a significant reduction of anxiety levels immediately after treatment. Subgroup analysis showed that only cranial electrotherapy stimulation had a significant effect on the reduction of anxiety levels among the three types of noninvasive brain stimulation., Conclusions: In individuals with spinal cord injury, no significant effects of noninvasive brain stimulation on neuropathic pain and depression were observed. Cranial electrotherapy stimulation may be beneficial for the management of anxiety. These findings do not support the routine use of noninvasive brain stimulation for neuropathic pain in individuals with spinal cord injury.

Objective: Transcranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)., Methods: We performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5-fold cross-validation. The primary outcome measures were the classification accuracy, precision, recall, and F1 score of TMS in differentiating each neurodegenerative disorder., Results: A total of 694 participants were included, namely 273 patients diagnosed as AD, 67 as DLB, and 207 as FTD, and 147 healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.89 to 0.92), high precision (0.86-0.92), high recall (0.93-0.98), and high F1 scores (0.89-0.95) in differentiating each neurodegenerative disorder., Interpretation: TMS is a noninvasive procedure that reliably and selectively distinguishes AD, DLB, FTD, and HC, representing a useful additional screening tool to be used in clinical practice. Ann Neurol 2020;87:394-404., (© 2020 American Neurological Association.)

Objectives: To evaluate the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT), and combining both treatments in a stepped care pathway for patients with treatment-resistant depression (TRD) in Ontario., Methods: A cost-utility analysis evaluated the lifetime costs and benefits to society of rTMS and ECT as first-line treatments for TRD using a Markov model, which simulates the costs and health benefits of patients over their lifetime. Health states included acute treatment, maintenance treatment, remission, and severe depression. Treatment efficacy and health utility data were extracted and synthesized from randomized controlled trials and meta-analyses evaluating these techniques. Direct costing data were obtained from national and provincial costing databases. Indirect costs were derived from government records. Scenario, threshold, and probabilistic sensitivity analyses were performed to test robustness of the results., Results: rTMS dominated ECT, as it was less costly and produced better health outcomes, measured in quality-adjusted life years (QALYs), in the base case scenario. rTMS patients gained an average of 0.96 additional QALYs (equivalent to approximately 1 year in perfect health) over their lifetime with costs that were $46,094 less than ECT. rTMS remained dominant in the majority of scenario and threshold analyses. However, results from scenarios in which the model's maximum lifetime allowance of rTMS treatment courses was substantially limited, the dominance of rTMS over ECT was attenuated. The scenario that showed the highest QALY gain (1.19) and the greatest cost-savings ($46,614) was when rTMS nonresponders switched to ECT., Conclusion: From a societal perspective utilizing a lifetime horizon, rTMS is a cost-effective first-line treatment option for TRD relative to ECT, as it is less expensive and produces better health outcomes. The reduced side effect profile and greater patient acceptability of rTMS that allow it to be administered more times than ECT in a patient's lifetime may contribute to its cost-effectiveness.

Background: Stimulus response curves (SR curves), measured using transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEP), yield important information regarding corticomotor connectivity. Limited understanding of SR curve analyses techniques for leg muscles after stroke may limit the utility of TMS data for walking recovery., Objective: To compare linear and non-linear curve fitting for MEP responses from the non-paretic and paretic tibialis anterior (TA) muscles., Methods: Accuracy of fit was measured using coefficient of determination (R 2 ). Similarities of the fit were compared using slopes and area under the curve (AUC)., Results: The non-linear function demonstrated higher R 2 and slopes. The AUC was not significantly different between the two analyses approaches. The non-linear non-paretic SR slopes and paretic AUC had significant associations with walking speed., Conclusion: Our results highlight the differences between non-linear and linear approaches to best fit the SR curves from bilateral TA muscles in stroke survivors. Although the linear function can appropriately fit the SR curve of the paretic and non-paretic TA, the non-linear function estimated a higher slope. We found the AUC to be a more robust measure that was not affected by the type of curve-fitting approach and only the AUC of the paretic TA showed significant association with walking speeds. A better understanding of SR curve fitting approaches for the TA muscles in individuals with chronic stroke allows for their optimal use in interpretation of TMS data and literature., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To investigate the efficacy and safety of non-invasive brain stimulation for fatigue in multiple sclerosis patients., Methods: We searched MEDLINE, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang databases up to October 25, 2018 (PROSPERO registration number: CRD42018112823). Randomized or pseudo-randomized, sham-controlled clinical trials evaluating the effect of non-invasive brain stimulation (NIBS) such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), transcranial random noise stimulation (tRNS), transcranial alternating current stimulation (tACS), cranial electrotherapy stimulation, and reduced impedance non-invasive cortical electrostimulation were included. Two authors independently performed data extraction and risk of bias assessment according to Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1. The primary outcome was fatigue scores before and after stimulation and the secondary outcome was adverse events., Results: Data from cross-over and parallel group studies were pooled using a generic inverse-variance approach. A total of 14 studies (11 for tDCS, 2 for TMS, and 1 for tRNS) recruiting 207 patients were included in the systematic review and meta-analysis. No eligible tACS, cranial electrotherapy stimulation or reduced impedance non-invasive cortical electrostimulation studies were found. Short-term and long-term treatment effects were significant for tDCS, whereas TMS and tRNS were not superior to sham stimulation. The available evidence supported the effectiveness of the 1.5 mA subgroup and bilateral S1 subgroup of tDCS. Adverse events were minor and transient but comparable between real and sham stimulation., Conclusions: tDCS is a safe and effective treatment for fatigue in MS patients. However, further studies are required to confirm our results in a large-scale population and to investigate the effectiveness of other NIBS subtypes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Non-invasive brain stimulation (NIBS) techniques have emerged as a promising tool for understanding and treating psychiatric disorders, necessitating a caution in terms of interpreting research results., Objective: This study aimed at systematically evaluating a representative sample of research conducted using NIBS interventions in neuro-psychiatric conditions, and assessing the power these studies achieved, given their sample sizes., Methods: A database search was conducted with defined keyword combinations. Using reported summary effects of the meta-analyses as estimate of the true effects, we calculated achieved power of each individual study to detect the effect indicated by the corresponding meta-analysis., Results: Findings suggest that mean and median powers in the field of NIBS were 0.50, with a mode at 0.83 (range 0.05-1.00). When analysed separately, the median powers were 0.27 for tDCS, 0.70 for TMS and 0.97 for ECT. These studies had a mean total sample size of 22.2 ± 24.9 subjects and the median reported effect size across all studies was 0.61., Conclusion: According to our findings, studies conducted in NIBS miss around 50% of true positive results. Further, it appears that most of the researchers in this field chase statistical significance with small sample sizes, thus compromising the quality of their conclusions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Low-frequency and high-frequency repetitive transcranial magnetic stimulation (rTMS) are similarly efficacious for treatment-resistant depression. Low-frequency is posited to be better tolerated than high-frequency rTMS, however, this is not supported by empirical evidence to date. This study aimed to quantify and compare the tolerability of low-versus high-frequency rTMS. Twenty healthy participants (mean age 38.6 ± 13.9 years) underwent low- and high-frequency rTMS administered on left frontal, fronto-central and central sites at 100% resting motor threshold. For the low-frequency protocol, 60 s of 1 Hz stimulation was applied at each site and for the high-frequency protocol, 3 × 5 s trains of 10 Hz stimulation with a 30 s inter-train interval were applied at each site. Tolerance for each stimulation type was assessed immediately after stimulation through participant ratings of overall intensity of scalp sensations, pain, muscle twitching, discomfort and any other sensation. Low-frequency rTMS was significantly less intense than high-frequency rTMS in overall intensity, pain, muscle twitching (all p < .01) and discomfort (p < .001). Limitations of this study include the healthy participant sample and administration of a single session of rTMS. While further work is needed in clinical samples using typical rTMS treatment protocols, these data provide the first evidence that low-frequency is better tolerated than high-frequency. These findings may inform clinical practice of rTMS treatment for depression (and other illnesses) by supporting the application of low-frequency protocols., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: The aim of this paper is to present the outcomes data from the largest United Kingdom's (UK) National Health Service (NHS) clinical rTMS service treating treatment resistant depression (TRD). Methods: The study was a retrospective investigation of routinely collected data on patients receiving rTMS between 2015 and 2017. Measures used were the clinician-rated Clinical Global Impression (CGI) and Hamilton Depression Rating Scale (HAM-D), and patient rated Beck Depression Inventory (BDI). The outcome data of 73 patients with TRD were analysed. The sample included patients with co-morbid psychiatric diagnosis. Results: Response and remission rates, respectively, were 40.4% and 25.5% for the HAM-D; 35.6% and 20.8% for the BDI; and 51.1% and 52.1% for the CGI. Effect sizes were medium (0.54, 0.52 and 0.56, respectively). Conclusions: The results show that a UK-based clinical service achieves similar results to those published internationally and that clinical rTMS can have significant impact on symptoms of depression in many patients with TRD. Health services are under pressure to make financial savings, investment in rTMS could reduce the long-term treatment costs associated with TRD.

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians'knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has broad diagnostic and therapeutic potential across a range of neurological and psychiatric diseases., Objective: This study utilises a bibliometric approach to systematically and comprehensively evaluate the literature on TMS from the last three decades., Methods: The Scopus citation database was used to identify all peer-reviewed journal articles concerning TMS over the period 1988-2017. Frequency-distribution, cross-tabulation and keyword analyses were performed to determine the most prolific researchers, institutions, nations, journals and the foremost studied disease entities within the TMS field. Given recent heightened awareness of gender bias across many fields of biomedicine, female representation among the most prolific authors was determined. Open-access publication rates and types of study design utilised were also quantified., Results: 17,492 TMS-related articles were published during the study period 1988-2017. The annual TMS research output has increased dramatically over this time, despite a recent levelling-off of publications per year. The most prolific institutions were based in the United Kingdom, the United States and Canada. The top disease entities studied were stroke, depression and Parkinson's disease. Only 4/52 of the most productive researchers during the study period were female. A minority (4.81%) of publications were published as gold open-access., Conclusion: This study implemented a systematic, bibliometric approach to quantitively assess the breadth of the TMS literature base and identify temporal publication and authorship trends. Drawing on these insights may aid understanding of historical progress in TMS over the last 30 years and help identify into unmet needs and opportunities to improve scientific and publishing practices to contribute to the future health of the field. These findings are likely to be relevant to researchers, clinicians, funders, industry collaborators and other stakeholders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: A study pertinent to the numerical modeling of cortical neurostimulation is conducted in an effort to compare the performance of the finite element method (FEM) and an original formulation of the boundary element fast multipole method (BEM-FMM) at matched computational performance metrics., Approach: We consider two problems: (i) a canonic multi-sphere geometry and an external magnetic-dipole excitation where the analytical solution is available and; (ii) a problem with realistic head models excited by a realistic coil geometry. In the first case, the FEM algorithm tested is a fast open-source getDP solver running within the SimNIBS 2.1.1 environment. In the second case, a high-end commercial FEM software package ANSYS Maxwell 3D is used. The BEM-FMM method runs in the MATLAB ® 2018a environment., Main Results: In the first case, we observe that the BEM-FMM algorithm gives a smaller solution error for all mesh resolutions and runs significantly faster for high-resolution meshes when the number of triangular facets exceeds approximately 0.25 M. We present other relevant simulation results such as volumetric mesh generation times for the FEM, time necessary to compute the potential integrals for the BEM-FMM, and solution performance metrics for different hardware/operating system combinations. In the second case, we observe an excellent agreement for electric field distribution across different cranium compartments and, at the same time, a speed improvement of three orders of magnitude when the BEM-FMM algorithm used., Significance: This study may provide a justification for anticipated use of the BEM-FMM algorithm for high-resolution realistic transcranial magnetic stimulation scenarios.

Background: The neurophysiology of major depressive disorder (MDD) has become a particular focus of transcranial magnetic stimulation (TMS) investigational studies. TMS combined with electroencephalography (TMS-EEG) affords a window to directly measure evoked activity from the dorsolateral prefrontal cortex (DLPFC), which is of considerable interest in MDD. Our study examined TMS-EEG responses from the DLPFC in persons with MDD compared with those in healthy participants. Specifically, we examined TMS-EEG markers linked to inhibitory and excitatory neurophysiological processes and their balance., Methods: In all, 30 participants with MDD and 30 age- and sex-matched healthy participants underwent single-pulse TMS-EEG to assess inhibition and excitation from DLPFC. TMS-EEG waveforms were analyzed through global mean field amplitude., Results: MDD participants demonstrated abnormalities in TMS-EEG markers in the DLPFC. Inhibitory measures-N45 and N100-were larger in the MDD group than in healthy participants (N45 [t = -4.894, p < .001] and N100 [t = -3.496, p = .001]). In a receiver operating characteristic analysis, N45 amplitude predicted depression illness state with 80% sensitivity, 73.3% specificity, and 76.6% accuracy (area under the curve = 0.829, p < .001). The global mean field amplitude area under the curve, a neurophysiological measure of cortical reactivity, was significantly larger in persons with MDD (t = -3.114, p = .003), as was P60 (t = -3.260, p = .002). In healthy participants, there was a positive correlation between inhibitory N45 and excitatory global mean field amplitude area under the curve (r = .711, p < .001) that was not present in persons with MDD (r = .149, p = .43), demonstrating a potential imbalance between inhibition and excitation in MDD., Conclusions: As the TMS-EEG waveform and its components index inhibitory and excitatory activity from the cortex, our results suggest abnormalities in these neurophysiological processes of DLPFC in persons with MDD., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: This study compared the effectiveness of regenerative injection therapy (RIT), i.e. prolotherapy, and repetitive transcranial magnetic stimulation (rTMS) in the treatment of fibromyalgia syndrome., Patients and Methods: This study included 120 female, age-matched fibromyalgia patients. All patients underwent a clinical examination, pain assessment by VAS, assessment of tender points, psychiatric and functional assessment using the Beck Depression Inventory (BDI), Fibromyalgia Impact Questionnaire Revised (RFIQ), and measurement of cortical auditory evoked potentials CAEPs elicited at 1000 Hz. Patients were divided into two equal groups; Group 1 received prolotherapy three times, two weeks apart, and Group 2 received rTMS sessions every other day for one month. Assessment was performed before treatment, immediately after treatment, and one month later., Results: A significant improvement of pain measured by the mean score of VAS was remarked in Group 1 compared to Group 2 immediately after treatment and one month later. There was statistically significant difference of mean scores for the number of tender points in Group 1 compared to Group 2 after treatment and one month later. The patients improved functionally, with a statistically significant difference in mean score of RFIQ, in Group 1 compared to Group 2 one month after treatment. However, there was a significant difference in mean score of BDI in Group 2 compared to Group 1 after treatment and one month later. Further, CAEPs showed better improvement, with a significant difference in Group 2, one month after treatment., Conclusion: RIT had the advantage in clinical and functional improvement in fibromyalgia patients, while rTMS had better results regarding depression and the cortical component of AEPs. These results might draw attention to the evaluability of a combination of both techniques for a better therapeutic response.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic reality in post-stroke rehabilitation. It has a neuroprotective effect on the modulation of neuroplasticity, improving the brain's capacity to retrain neural circuits and promoting restoration and acquisition of new compensatory skills., Development: We conducted a literature search on PubMed and also gathered the latest books, clinical practice guidelines, and recommendations published by the most prominent scientific societies concerning the therapeutic use of rTMS in the rehabilitation of stroke patients. The criteria of the International Federation of Clinical Neurophysiology (2014) were followed regarding the inclusion of all evidence and recommendations., Conclusions: Identifying stroke patients who are eligible for rTMS is essential to accelerate their recovery. rTMS has proven to be safe and effective for treating stroke complications. Functional brain activity can be optimised by applying excitatory or inhibitory electromagnetic pulses to the hemisphere ipsilateral or contralateral to the lesion, respectively, as well as at the level of the transcallosal pathway to regulate interhemispheric communication. Different studies of rTMS in these patients have resulted in improvements in motor disorders, aphasia, dysarthria, oropharyngeal dysphagia, depression, and perceptual-cognitive deficits. However, further well-designed randomized controlled clinical trials with larger sample size are needed to recommend with a higher level of evidence, proper implementation of rTMS use in stroke subjects on a widespread basis., (Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Schizophrenia is a mental disorder with significant socioeconomic burden. Although current pharmacological treatments are effective for treating positive symptoms, medications have little-to-no effect in the treatment of negative symptoms., Objective: To assess the efficacy of non-invasive brain stimulation (NIBS) for negative symptoms in schizophrenia in randomized clinical trials (RCTs)., Methods: A systematic review in Medline and Cochrane Library databases was performed up to May 31, 2017. The primary outcome was Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I 2 and χ 2 tests. Publication bias was assessed using Begg's funnel plot., Results: 31 RCTs (n = 1272) were included, most with small-to-modest sample sizes. Both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were superior to sham (Hedges' g = 0.19; 95% CI 0.07-0.32; and 0.5; 0.02-0.97, respectively). Only one study evaluated the use of transcutaneous auricular vagus nerve stimulation (taVNS). The funnel plot and Eggers test showed that the risk of publication bias was low. In relation to heterogeneity, we found an I 2 of 0% (p = 0.749) and 51.3% (0.055) for rTMS and tDCS, respectively., Conclusion: Both rTMS and tDCS were superior to sham stimulation for ameliorating negative symptoms in schizophrenia. We found no considerable heterogeneity or publication bias in our analysis, corroborating the strength of our findings. Not enough studies on other NIBS techniques, such as taVNS, were found for an isolated analysis. Further RCTs with larger sample sizes are needed to clarify the specific impact of NIBS on negative symptoms in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Data and best practice recommendations for transcranial magnetic stimulation (TMS) use in adults are largely available. Although there are fewer data in pediatric populations and no published guidelines, its practice in children continues to grow., Methods: We performed a literature search through PubMed to review all TMS studies from 1985 to 2016 involving children and documented any adverse events. Crude risks were calculated per session., Results: Following data screening we identified 42 single-pulse and/or paired-pulse TMS studies involving 639 healthy children, 482 children with central nervous system disorders, and 84 children with epilepsy. Adverse events occurred at rates of 3.42%, 5.97%, and 4.55% respective to population and number of sessions. We also report 23 repetitive TMS studies involving 230 central nervous system and 24 children with epilepsy with adverse event rates of 3.78% and 0.0%, respectively. We finally identified three theta-burst stimulation studies involving 90 healthy children, 40 children with central nervous system disorder, and no epileptic children, with adverse event rates of 9.78% and 10.11%, respectively. Three seizures were found to have occurred in central nervous system disorder individuals during repetitive TMS, with a risk of 0.14% per session. There was no significant difference in frequency of adverse events by group (P = 0.988) or modality (P = 0.928)., Conclusions: Available data suggest that risk from TMS/theta-burst stimulation in children is similar to adults. We recommend that TMS users in this population follow the most recent adult safety guidelines until sufficient data are available for pediatric specific guidelines. We also encourage continued surveillance through surveys and assessments on a session basis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Despite growing evidence supporting the clinical interest of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD), little is known regarding the effects of clinical and sociodemographic factors on the clinical outcome in patients., Methods: We retrospectively investigated the effects of clinical (using the 3-factor model of the Montgomery-Åsberg depression rating scale [MADRS] encompassing dysphoria, retardation and vegetative symptoms) and sociodemographic characteristics of participants on clinical outcome in a sample of 54 TRD patients receiving low frequency rTMS (1Hz, 360 pulses) applied over the right dorsolateral prefrontal cortex combined with sham venlafaxine., Results: Responders (n=29) displayed lower retardation baseline scores (13.6±2.9) than non-responders (15.6±2.9; n=25; P=0.02). We also observed a significant difference between the numbers of ex-smokers in responders and non-responders groups; all ex-smokers (n=8) were responders to rTMS (P=0.005)., Conclusion: Low MADRS retardation factor and ex-smoker status is highly prevalent in responders to low frequency rTMS. Further studies are needed to investigate the predictive value of these factors., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The repetitive transcranial magnetic stimulation (TMS) opens new therapeutic options in neuropsychiatric disorders. The use of rTMS in depressive disorders has been most preferably investigated in clinical trials. In Germany, the application of rTMS outside of clinical trials is already increasingly common, not only for depression. Our nationwide survey in psychiatric hospitals was used to detect the current state of the application of rTMS in clinical practice, and should serve as a basis for the development of quality standards., (© Georg Thieme Verlag KG Stuttgart · New York.)

To build an understanding of the neurobiology underpinning arm recovery in people with severe arm impairment due to stroke, we conducted a pooled individual data systematic review to: 1) characterize brain biomarkers; 2) determine relationship(s) between biomarkers and motor outcome; and 3) establish relationship(s) between biomarkers and motor recovery. Three electronic databases were searched up to October 2, 2015. Eligible studies included adults with severe arm impairment after stroke. Descriptive statistics were calculated to characterize brain biomarkers, and pooling of individual patient data was performed using mixed-effects linear regression to examine relationships between brain biomarkers and motor outcome and recovery. Thirty-eight articles including individual data from 372 people with severe arm impairment were analysed. The majority of individuals were in the chronic (> 6 months) phase post stroke (51%) and had a subcortical stroke (49%). The presence of a motor evoked potential (indexed by transcranial magnetic stimulation) was the only biomarker related to better motor outcome ( p  = 0.02). There was no relationship between motor outcome and stroke volume (cm 3 ), location (cortical, subcortical, mixed) or side (left vs. right), and corticospinal tract asymmetry index (extracted from diffusion weighted imaging). Only one study had longitudinal data, thus no data pooling was possible to address change over time (preventing our third objective). Based on the available evidence, motor evoked potentials at rest were the only biomarker that predicted motor outcome in individuals with severe arm impairment following stroke. Given that few biomarkers emerged, this review highlights the need to move beyond currently known biomarkers and identify new indices with sufficient variability and sensitivity to guide recovery models in individuals with severe motor impairments following stroke., Prospero: CRD42015026107.

Background: The short-term beneficial effects of repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease (PD) have been addressed by previous meta-analyses while its long-term effects remain undetermined. Although deterioration of walking and upper limb function greatly affects the participation in activities and quality of life of PD sufferers, the effect of rTMS thereon has not been systematically studied., Objective: This systematic review aimed to examine the efficacy of rTMS on improving physical function and motor signs over the short- and long-terms in people with PD., Methods: Five electronic databases were systematically searched for English language full-text articles using relevant search terms. Only randomized placebo-controlled trials investigating the effects of rTMS in PD were considered. The primary outcomes were walking performance, upper limb function, and unified Parkinson's disease rating scale (UPDRS) section III. Trials with similar outcomes were pooled by calculating Hedges' g using random-effects model., Results: Twenty-two trials comprising 555 people with PD were included. Pooled estimates of effect of rTMS indicated significantly improved short-term upper limb function (Hedges' g, 0.40, P = 0.007), short-term (Hedges' g, 0.61, P = 0.03) and long-term walking performance (Hedges' g, 0.89, P = 0.03), short-term (Hedges' g, 0.31, P = 0.003) and long-term (Hedges' g, 0.54, P = 0.003) UPDRS III scores. Subgroup analyses suggest a more prominent effect for M1 stimulation. Meta-regression revealed that a greater number of total stimulation pulses were associated with more UPDRS III improvements over the long-term., Conclusion: The pooled evidence suggests that rTMS improves upper limb function in the short-term, walking performance and UPDRS III in the short- and long-terms in PD sufferers. Further studies are required to develop optimal rTMS therapeutic protocols for PD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Modern neuromodulatory techniques for military applications have been explored for the past decade, with an intent to optimize operator performance and, ultimately, to improve overall military effectiveness. In light of potential military applications, some researchers have voiced concern about national security agency involvement in this area of research, and possible exploitation of research findings to support military objectives. The aim of this article is to examine the U.S. Department of Defense's interest in and application of neuromodulation., Methods: We explored articles, cases, and historical context to identify critical considerations of debate concerning dual use (i.e., national security and civilian) technologies, specifically focusing on non-invasive brain stimulation (NIBS)., Discussion: We review the background and recent examples of DoD-sponsored neuromodulation research, framed in the more general context of research that aims to optimize and/or rehabilitate human performance. We propose that concerns about military exploitation of neuromodulatory science and technology are not unique, but rather are part of a larger philosophic debate pertaining to military application of human performance science and technology. We consider unique aspects of the Department of Defense research enterprise--which includes programs crucial to the advancement of military medicine--and why it is well-situated to fund and perform such research. We conclude that debate concerning DoD investment in human performance research must recognize the significant potential for dual use (civilian, medical) benefit as well as the need for civilian scientific insight and influence. Military interests in the health and performance of service members provide research funding and impetus to dual use applications that will benefit the civilian community., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The clinical, social and financial burden of autism spectrum disorder (ASD) is staggering. We urgently need valid and reliable biomarkers for diagnosis and effective treatments targeting the often debilitating symptoms. Transcranial magnetic stimulation (TMS) is beginning to be used by a number of centers worldwide and may represent a novel technique with both diagnostic and therapeutic potential. Here we critically review the current scientific evidence for the use of TMS in ASD. Though preliminary data suggests promise, there is simply not enough evidence yet to conclusively support the clinical widespread use of TMS in ASD, neither diagnostically nor therapeutically. Carefully designed and properly controlled clinical trials are warranted to evaluate the true potential of TMS in ASD.

Transcranial magnetic stimulation (TMS) is a method based on the excitation of neurons in the brain cortex by an alternating magnetic field. Repetitive TMS (rTMS) is a kind of stimulation, in which a series of pulses are generated. rTMS can modulate different cortical area's activity and change their interactions using different protocols. The review shows the application of rTMS in treatment of various neurological (stroke, Parkinson's disease, dystonia, chronic pain syndromes, tinnitus, epilepsy, spasticity syndrome) and psychiatric (depression and anxiety) disorders. Authors collected all the main protocols, and gave recommendations for their use in clinical practice according to principles of evidence medicine.

The aim of this paper was to present the current use of repetitive transcranial magnetic stimulation (rTMS) in psychiatric disorders with the mode of its application and results of most prominent studies. The most robust data concerns its use in major depressive disorder, while in other psychiatric disorders results are preliminary. TMS with the development of new techniques and new treatment protocols has a potential to become a very useful treatment tool in pharmacoresistant patients or patients intolerant of pharmacotherapy.

Background: In transcranial magnetic stimulation (TMS), the stimulation-coil current is typically increased from 0 to over 5000 A in less than 100 μs. At the peak current, the energy stored in the magnetic field is over 300 J. Thus, the average power during a pulse exceeds 3 MW; the stimulator needs to be built from high-power electronics. The power requirements often limit the duration and frequency of repetitive TMS, for example, via coil heating., Objective: We introduce a method for finding the minimum-energy solution for a TMS coil with given focality constraints., Methods: This optimization is performed by using a spherically symmetric head model and by expressing the coil as a continuous surface current density, which is eventually discretized to form the coil windings. For the optimization, we defined TMS focality separately for the directions parallel and perpendicular to the field direction at the maximum of induced electric field., Results: The computational model used for optimization was verified by manufacturing a prototype coil and measuring the electric field it induces in a spherically symmetric conductor. The optimized coil design requires significantly less power than existing TMS coil designs (a 73% reduction compared to an existing TMS coil with similar focality)., Conclusion: The described method allows for more efficient, more focal TMS coils, which may reduce coil heating and the coil click., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)