The Efficacy and Safety of Different Noninvasive Therapies in the Treatment of Central Poststroke Pain (CPSP): A Network Meta-Analysis and Systematic Review.

OBJECTIVE: To evaluate the efficacy and safety of noninvasive therapies in the treatment of central poststroke pain (CPSP) by network meta-analysis and to provide an evidence-based basis for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, Wanfang, and VIP were searched for clinical randomized controlled studies on noninvasive therapy for CPSP. The retrieval time limit was from the establishment of each database to July 2022. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included randomized controlled trials (RCTs). Stata 14.0 was used for network meta-analysis, and Review Manager 5.3 software was used for traditional meta-analysis. RESULTS: Twelve RCTs involving 8 treatment schemes and 641 patients were finally included. The results of the network meta-analysis showed the following rankings in visual analysis scale (VAS): super laser injury on stellate ganglia (SLI) > transcranial direct current stimulation (tDCS) > music therapy (MT) > repetitive transcranial magnetic stimulation (rTMS) > continuous theta burst stimulation (cTBS) > transcutaneous acupoint electrical stimulation (TAES) > common therapy (CT). The total clinical efficiency ranked as follows: psychological training of mindfulness (PT) > rTMS > CT. Clinical adverse reactions ranked as follows: rTMS > MT > CT > SLI. CONCLUSIONS: Noninvasive complementary therapy can effectively alleviate the pain of CPSP patients, and the efficacy and safety of SLI are relatively significant. However, due to the limitations of this study, the efficacy ranking cannot fully explain the advantages and disadvantages of clinical efficacy. In the future, more multicentre, large sample, double-blind clinical randomized controlled trials are needed to supplement and demonstrate the results of this study.

Impact of transcranial magnetic stimulation on motor function in children with acquired brain injury: a scoping review protocol.

BACKGROUND: Children with severe acquired brain injury (ABI) require early and effective neurorehabilitation provision to promote a good long-term functional outcome. Transcranial magnetic stimulation (TMS) has been used to improve motor skills for children with cerebral palsy but there is limited material supporting its use in children with ABI who have a motor disorder. OBJECTIVE: To systematically answer what the TMS intervention effects are on motor function in children with ABI as reported in the literature. METHODS AND ANALYSIS: This scoping review will follow Arksey and O'MaIIey's scoping review methodological framework. A comprehensive computerised bibliographic databases search will be performed in MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine, BNI, Ovid Emcare, PsyclNFO, Physiotherapy Evidence Database, Cochrane Central Register using keywords related to TMS and children with ABI.Studies that examine the effect of TMS intervention on motor function as either a primary or secondary objective will be included for this review. Study design and publication detail, participant demographic details, type and severity of ABI and other clinical information, TMS procedure, associated therapy intervention, comparator/control parameters and the outcome measure used data will be gathered.The International Classification of Functioning, Disability and Health for Children and Youth framework will be used to report the TMS effect in children with ABI. A narrative synthesis of the findings describing the therapeutic effects of TMS intervention, limitations and adverse effects will be synthesised and reported. This review will help to summarise the existing knowledge base and to guide further research areas. This review outcome may help to evolve therapists' role to next-generation technology-based neurorehabilitation programmes. ETHICS AND DISSEMINATION: No ethical approval is required for this review as we will be collecting data from previously published studies. We will present the findings at scientific conferences and publish in a peer-review journal.

Effect of high-frequency repetitive transcranial magnetic stimulation under different intensities upon rehabilitation of chronic pelvic pain syndrome: protocol for a randomized controlled trial.

INTRODUCTION: Nearly one in seven women worldwide suffers from chronic pelvic pain syndrome (CPPS) each year. Often, CPPS necessitates a combination of treatments. Studies have shown the good therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) upon CPPS. We wish to undertake a randomized controlled trial (RCT) to observe the effect of high-frequency rTMS at different intensities upon CPPS. METHODS AND ANALYSES: In this prospective, double-blinded RCT, 63 female CPPS participants will be recruited and randomized (1:1:1) to high-intensity rTMS, low-intensity rTMS, or sham rTMS. The control group will receive a 10-day course of conventional pelvic floor (PF) rehabilitation (neuromuscular stimulation, magnetic therapy, or light therapy of the PF). On the basis of conventional treatment, participants in the high-intensity rTMS group will receive pulses of 10 Hz with a resting motor threshold (RMT) of 110% for a total of 15,000 pulses. Participants in the low-intensity rTMS group will receive pulses of 10 Hz with an RMT of 80% with 15,000 pulses. The sham rTMS group will be subjected to sham stimulation with the same sound as produced by the real magnetic stimulation coil. The primary outcome will be determined using a visual analog scale, the Genitourinary Pain Index, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale. The secondary outcome will be determined by electromyography of the surface of PF muscles at baseline and after treatment completion. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of Bao'an People's Hospital, Shenzhen, Guangdong Province (approval number: BYL20211203). The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences (Protocol version 1.0-20220709). TRIAL REGISTRATION: Chictr.org.cn, ID: ChiCTR2200055615. Registered on 14 January 2022, http://www.chictr.org.cn/showproj.aspx?proj=146720 . Protocol version 1.0-20220709.

Unwanted effects of treatments for depression in children and adolescents: a mapping of systematic reviews.

OBJECTIVES: To describe the results of a mapping review exploring the coverage of unwanted treatment effects in systematic reviews of the effects of various treatments for moderate to severe depression in children and adolescents. SETTING: Any context or service providing treatment for depression, including interventions delivered in local communities and school settings, as well as services provided in primary or specialist care. PARTICIPANTS: Children and young people with moderate to severe depression (<18 years). INTERVENTIONS: Systematic reviews published in 2011 or later comparing the effects of any treatment for children and adolescents with moderate to severe depression meeting the Database of Abstracts of Reviews of Effects criteria. The systematic search was performed in April 2018 and updated in December 2018. PRIMARY OUTCOMES: Any unwanted effects of treatments as defined in the systematic review. RESULTS: We included 10 systematic reviews covering 19 treatment comparisons. Unwanted effects were assessed for seven of 19. Three comparisons were evaluations of pharmaceutical interventions or combination therapy, reporting effects on 'suicidal ideation' and 'suicide risk'. Two included therapy, reporting 'self-harm', and 'suicidal ideation', and two comparisons included transcranial magnetic stimulation and electroconvulsive treatment. Unwanted effects evaluated for these treatments were mostly symptoms of physical discomfort such as headache or cramps. For the remaining treatment comparisons evaluating psychological and psychosocial therapies, unwanted effects were not evaluated or found. A limitation of overviews of systematic reviews such as this mapping study is that data extraction is done based on the reporting of results by the review authors and not on the primary studies. CONCLUSION: The unwanted effects of widely used treatments for children and young people with depression is unknown. This is a major barrier for evidence informed decision making about treatment choices for children and young people. We suggest that unwanted effects should be a reporting standard in all protocols describing evaluations of treatments, including primary studies as well as systematic reviews.

Non-invasive brain stimulation for fatigue in multiple sclerosis patients: A systematic review and meta-analysis.

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.

A multi-scale computational approach based on TMS experiments for the assessment of electro-stimulation thresholds of the brain at intermediate frequencies.

In recent years, human exposure to electromagnetic fields (EMF) at intermediate frequencies (300 Hz-10 MHz) has risen, mainly due to the growth of technologies using these fields. The current safety guidelines/standards defined by international bodies (e.g. ICNIRP and IEEE) established basic restrictions for limiting EMF exposure. These limits at intermediate frequencies are derived from threshold values of the internal electric field that may produce transient effects, such as the stimulation of the nervous system. However, there are some discrepancies between the basic restrictions of those guidelines/standards. The aim of this study is to investigate the excitation thresholds of the nervous system exposed to intermediate-frequency electromagnetic fields, with the purpose of extrapolating the threshold-frequency curves which are compared with existing basic restrictions prescribed by the international guidelines/standards. Our investigation was based on transcranial magnetic stimulation (TMS) experiments, physiological measurements, and individualized MRI-based computer simulations for the determination of brain stimulation thresholds. The combined approach with established biological axon models enabled the extrapolation of the measured thresholds for sinusoidally varying electric fields. The findings reveal that the exposure limits are significantly conservative for the brain, especially at frequencies in the range of 300 Hz-5 kHz.

Repetitive transcranial magnetic stimulation therapy for motor recovery in Parkinson's disease: A Meta-analysis.

INTRODUCTION: Therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor recovery of Parkinson's disease (PD) have been reported; however, the protocols of these studies varied greatly. The aim of this meta-analysis was to evaluate the optimal rTMS parameters for motor recovery of PD. METHODS: Electronic databases were searched for studies investigating the therapeutic effects of rTMS on motor function in patients with PD. The section III of the Unified Parkinson's Disease Rating Scale (UPDRS) was extracted as the primary outcome, and the standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. RESULTS: Twenty-three studies with a total of 646 participants were included. The pooled estimates of rTMS revealed significant short-term (SMD, 0.37; p < 0.00001) and long-term (SMD, 0.39; p = 0.005) effects on motor function improvement of PD. Subgroup analysis observed that high-frequency rTMS (HF-rTMS) was significant in improving motor function (SMD, 0.48; p < 0.00001), but low-frequency rTMS (LF-rTMS) was not. In particular, when HF-rTMS targeted over the primary motor cortex (M1), in which the bilateral M1 revealed a larger effect size than unilateral M1. Compared to single-session, multi-session of HF-rTMS over the M1 showed significant effect size. In addition, HF-rTMS over the M1 with a total of 18,000-20,000 stimulation pulses yielded more significant effects (SMD, 0.97; p = 0.01) than other dosages. CONCLUSIONS: In conclusion, multi-session of HF-rTMS over the M1 (especially bilateral M1) with a total of 18,000-20,000 pulses appears to be the optimal parameters for motor improvement of PD.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables. MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events. AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.

Abnormal brain oscillations persist after recovery from bipolar depression.

When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20-40Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21-50Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11-27Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.

Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease.

Alzheimer's disease (AD) is a looming public health crisis that currently lacks an effective treatment. Noninvasive Brain Stimulation (NBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offers a promising alternative approach to pharmacological interventions for an increasing number of neurological and psychiatric conditions. The aim of this review is summarize data from therapeutic trials of NBS in AD and other dementing illnesses. Despite the potential of NBS, there is limited theoretical framework and a lack of guidelines for its applications to AD. Several published clinical trials failed to report key parameters of the interventions thus limiting the utility of the study to assess efficacy and safety. Our review concludes with some suggestions for future studies aimed to advance research into NBS as a potential treatment for the symptoms and disabilities caused by AD and to enable comparison of results across trials. Ultimately, appropriately powered, and controlled, multi-site randomized clinical trials will be needed to evaluate the therapeutic potential of NBS in AD.

Scalp acupuncture and electromagnetic convergence stimulation for patients with cerebral infarction: study protocol for a randomized controlled trial.

BACKGROUND: Scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS) are effective for treating cerebral infarction. This study aims to examine the efficacy and safety of SA and electromagnetic convergence stimulation (SAEM-CS), which was developed through collaboration between conventional medical physicians and doctors who practice traditional Korean medicine. SAEM-CS was designed to improve function in patients with cerebral infarction, compared to the improvement after conventional stroke rehabilitation, SA, and rTMS therapeutic approaches. METHODS/DESIGN: This study is a prospective, outcome assessor-blinded, randomized controlled clinical trial with a 1:1:1:1 allocation ratio. Participants with motion or sensory disabilities caused by a first-time cerebral infarction (n = 60) that had occurred within 1 month of the study onset will be randomly assigned to control, SA, rTMS, or SAEM-CS groups. All groups will receive two sessions of conventional rehabilitation treatment per day. The SA group will receive SA on the upper limb area of MS6 and MS7 (at the lesional hemisphere) for 20 min, the rTMS group will receive low-frequency rTMS (LF-rTMS) treatment on the hot spot of the M1 region (motor cortex at the contralesional hemisphere) for 20 min, and the SAEM-CS group will receive LF-rTMS over the contralesional M1 region hot spot while receiving simultaneous SA stimulation on the lesional upper limb area of MS6 and MS7 for 20 min. SA, rTMS, and SAEM-CS treatments will be conducted once/day, 5 days/week (excluding Saturdays and Sundays) for 3 weeks, for a total of 15 sessions. The primary outcome will be evaluated using the Fugl-Meyer Assessment, while other scales assessing cognitive function, activities of daily living, walking, quality of life, and stroke severity are considered secondary outcome measures. Outcome measurements will be conducted at baseline (before intervention), 3 weeks after the first intervention (end of intervention), and 4 weeks after intervention completion. DISCUSSION: This study aims to explore the efficacy and safety of SAEM-CS on cerebral infarction. Collaborative research combined traditional Korean and conventional medicines, which can be useful in developing new treatment technologies. TRIAL REGISTRATION: KCT0001768 . Registered on 14 January 2016.

Non-invasive brain stimulation techniques for chronic pain.

BACKGROUND: This is an updated version of the original Cochrane review published in 2010, Issue 9. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain. SEARCH METHODS: We searched CENTRAL (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials registers. The original search for the review was run in November 2009 and searched all databases from their inception. To identify studies for inclusion in this update we searched from 2009 to July 2013. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS or RINCE if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. DATA COLLECTION AND ANALYSIS: Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis. We used the GRADE system to summarise the quality of evidence for core comparisons. MAIN RESULTS: We included an additional 23 trials (involving 773 participants randomised) in this update, making a total of 56 trials in the review (involving 1710 participants randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS studies). We judged only three studies as being at low risk of bias across all criteria.Meta-analysis of studies of rTMS (involving 528 participants) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective (low-quality evidence) and that rTMS applied to the dorsolateral prefrontal cortex is ineffective (very low-quality evidence). We found a short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies (low-quality evidence, standardised mean difference (SMD) 0.39 (95% confidence interval (CI) -0.27 to -0.51 P < 0.01)). This equates to a 12% (95% CI 8% to 15%) reduction in pain, which does not exceed the pre-established criteria for a minimal clinically important difference (≥ 15%). Evidence for multiple-dose studies was heterogenous but did not demonstrate a significant effect (very low-quality evidence).For CES (six studies, 270 participants) no statistically significant difference was found between active stimulation and sham (low-quality evidence).Analysis of tDCS studies (11 studies, 193 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation (very low-quality evidence). Pre-specified subgroup analysis of tDCS applied to the motor cortex (n = 183) did not demonstrate a statistically significant effect and this lack of effect was consistent for subgroups of single or multiple-dose studies.One small study (n = 91) at unclear risk of bias suggested a positive effect of RINCE over sham stimulation on pain (very low-quality evidence).Non-invasive brain stimulation appears to be frequently associated with minor and transient side effects, though there were two reported incidences of seizure related to active rTMS in the included studies. AUTHORS' CONCLUSIONS: Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. It is likely that multiple sources of bias may exaggerate this observed effect. The effects do not meet the predetermined threshold of minimal clinical significance and multiple-dose studies do not consistently demonstrate effectiveness. The available evidence suggests that low-frequency rTMS, rTMS applied to the pre-frontal cortex, CES and tDCS are not effective in the treatment of chronic pain. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation and the conclusion regarding the effectiveness of tDCS has changed. We recommend that previous readers should re-read this update. There is a need for larger, rigorously designed studies, particularly of longer courses of stimulation. It is likely that future evidence may substantially impact upon the presented results.

[Related noise exposure and auditory consequence during transcranial magnetic stimulation: new insights and review of the literature]. / Exposition sonore et répercussions auditives au cours de la stimulation magnétique transcrânienne répétitive: données récentes et revue de la littérature.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation tool with increasing therapeutic applications in neurology, psychiatry and in the treatment of chronic tinnitus, and with a growing interest in cognitive neuroscience. One of its side effects is the loud click sound generated simultaneously to the magnetic pulse, which depends both on the equipment and rTMS intensity. This impulse sound could transiently modify peripheral hearing mechanisms, and hence hearing thresholds, both in patients and in rTMS practitioners. Furthermore, if no precautions are taken, especially in subjects with several risks factors for hearing loss, it is possible that the repetition of exposure could lead to more definitive changes in hearing thresholds. These issues are often neglected, although they could have specific relevance in rTMS treatment for tinnitus or in auditory cognitive neuroscience. This review specifically deals with noise exposure during rTMS and its potential consequences on the auditory system. It provides several practical solutions to help minimize exposure.

Stroke rehabilitation using noninvasive cortical stimulation: motor deficit.

Noninvasive cortical stimulation (NICS) has been used during the acute, postacute and chronic poststroke phases to improve motor recovery in stroke patients having upper- and/or lower-limb paresis. This paper reviews the rationale for using the different NICS modalities to promote motor stroke rehabilitation. The changes in cortical excitability after stroke and the possible mechanisms of action of cortical stimulation in this context are outlined. A number of open and placebo-controlled trials have investigated the clinical effect of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) of the primary motor cortex in patients with motor stroke. These studies attempted to improve motor performance by increasing cortical excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and to then restore a normal balance of interhemispheric inhibition. All these NICS techniques administered alone or in combination with various methods of neurorehabilitation were found to be safe and equally effective at the short term on various aspects of poststroke motor abilities. However, the long-term effect of NICS on motor stroke needs to be further evaluated before considering the use of such a technique in the daily routine management of stroke.

Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain injury.

OBJECTIVE: To review the use of noninvasive brain stimulation (NBS) as a therapeutic tool to enhance neuroplasticity following traumatic brain injury (TBI). MATERIALS AND METHODS: Based on a literature search, we describe the pathophysiological events following TBI and the rationale for the use of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in this setting. RESULTS: The pathophysiological mechanisms occurring after TBI vary across time and therefore require differential interventions. Theoretically, given the neurophysiological effects of both TMS and tDCS, these tools may: 1) decrease cortical hyperexcitability acutely after TBI; 2) modulate long-term synaptic plasticity as to avoid maladaptive consequences; and 3) combined with physical and behavioral therapy, facilitate cortical reorganization and consolidation of learning in specific neural networks. All of these interventions may help decrease the burden of disabling sequelae after brain injury. CONCLUSIONS: Evidence from animal and human studies reveals the potential benefit of NBS in decreasing the extent of injury and enhancing plastic changes to facilitate learning and recovery of function in lesioned neural tissue. However, this evidence is mainly theoretical at this point. Given safety constraints, studies in TBI patients are necessary to address the role of NBS in this condition as well as to further elucidate its therapeutic effects and define optimal stimulation parameters.

Low-frequency repetitive TMS plus anodal transcranial DCS prevents transient decline in bimanual movement induced by contralesional inhibitory rTMS after stroke.

BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected motor cortex may improve motor function of the paretic hand after stroke. However, low-frequency rTMS might adversely affect bimanual movement by decreasing transcallosal function. OBJECTIVE: The authors investigated whether combined administration of rTMS and transcranial direct current stimulation (tDCS) prevents deterioration of bimanual movement induced by low-frequency rTMS over the unaffected hemisphere. METHODS: A total of 27 participants with chronic subcortical stroke were randomly assigned to receive either 1 Hz rTMS over the unaffected hemisphere, anodal tDCS over the affected hemisphere, or a combination of rTMS and tDCS. All patients performed a pinching motor-training task after stimulation. Bimanual movement and transcallosal inhibition (TCI) were evaluated after stimulation. RESULTS: rTMS and rTMS-tDCS enhanced the motor training effect on the paretic hand. rTMS decreased bimanual coordination and reduced TCI from the unaffected to the affected hemisphere (TCI(unaff-aff)). rTMS-tDCS changed TCI balance of both hemispheres but did not affect bimanual coordination or TCI(unaff-aff). The change in bimanual coordination was negatively correlated with TCI(unaff-aff). Following stimulation, improvement in the pinch force in the paretic hand was negatively correlated with TCI balance. CONCLUSIONS: Inhibitory rTMS over the unaffected hemisphere transiently caused deterioration of bimanual movements for the current task in stroke patients. This short-term decline was prevented by combined administration of low-frequency rTMS over the unaffected hemisphere and anodal tDCS over the affected hemisphere. These responses to bihemispheric stimulation suggest possible caution and opportunities for the rehabilitation of hand function after stroke.

The promises and perils of non-invasive brain stimulation.

Non-invasive brain stimulation promises innovative experimental possibilities for psychology and neuroscience as well as new therapeutic and palliative measures in medicine. Because of its good risk-benefit ratio, non-invasiveness and reversibility as well as its low effort and cost it has good chances of becoming a widespread tool in science, medicine and even in lay use. While most issues in medical and research ethics such as informed consent, safety, and potential for misuse can be handled with manageable effort, the real promise of brain stimulation does raise one prominent moral worry: it may lay the foundation of reliable, precise and stable manipulations of the mind. This article addresses this worry and concludes that it is not the possibility of manipulation, but the shift in our understanding of our mind which stands in need of careful consideration.

Noninvasive brain stimulation in traumatic brain injury.

OBJECTIVE: To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). METHODS: Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. MAIN FINDINGS: We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. CONCLUSIONS: Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.

The emerging use of brain stimulation treatments for psychiatric disorders.

OBJECTIVE: The aim of this study was to review the current state of development and application of a wide range of brain stimulation approaches in the treatment of psychiatric disorders. METHOD: The approaches reviewed include forms of minimally invasive magnetic and electrical stimulation, seizure induction, implanted devices and several highly novel approaches in early development. RESULTS: An extensive range of brain stimulation approaches are now being widely used in the treatment of patients with psychiatric disorders, or actively investigated for this use. Both vagal nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) have been introduced into clinical practice in some countries. A small body of research suggests that VNS has some potentially long-lasting antidepressant effects in a minority of patients treated. rTMS has now been extensively investigated for over 15 years, with a large body of research now supporting its antidepressant effects. Further rTMS research needs to focus on defining the most appropriate stimulation methods and exploring its longer term use in maintenance protocols. Very early data suggest that magnetic seizure therapy (MST) has promise in the treatment of patients referred for electroconvulsive therapy: MST appears to have fewer side effects and may have similar efficacy. A number of other approaches including surgical and alternative forms of electrical stimulation appear to alter brain activity in a promising manner, but are in need of evaluation in more substantive patient samples. CONCLUSIONS: It appears likely that the range of psychiatric treatments available for patients will grow over the coming years to progressively include a number of novel brain stimulation techniques.