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Neurological and psychiatric diseases generally have no cure, so innovative non-pharmacological treatments, including non-invasive brain stimulation, are interesting therapeutic tools as they aim to trigger intrinsic neural repair mechanisms. A common brain stimulation technique involves the application of pulsed magnetic fields to affected brain regions. However, investigations of magnetic brain stimulation are complicated by the use of many different stimulation parameters. Magnetic brain stimulation is usually divided into two poorly connected approaches: (1) clinically used high-intensity stimulation (0.5–2 Tesla, T) and (2) experimental or epidemiologically studied low-intensity stimulation (μT–mT). Human tests of both approaches are reported to have beneficial outcomes, but the underlying biology is unclear, and thus optimal stimulation parameters remain ill defined. Here, we aim to bring together what is known about the biology of magnetic brain stimulation from human, animal, and in vitro studies. We identify the common effects of different stimulation protocols; show how different types of pulsed magnetic fields interact with nervous tissue; and describe cellular mechanisms underlying their effects—from intracellular signalling cascades, through synaptic plasticity and the modulation of network activity, to long-term structural changes in neural circuits. Recent advances in magneto-biology show clear mechanisms that may explain low-intensity stimulation effects in the brain. With its large breadth of stimulation parameters, not available to high-intensity stimulation, low-intensity focal magnetic stimulation becomes a potentially powerful treatment tool for human application.

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier—NCT03774927.

Randomised and sham-controlled trials (RCTs) of repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) have yielded conflicting results, which may be due to the variability in rTMS parameters used. We performed an updated systematic review and meta-analysis on the effectiveness of rTMS for the treatment of OCD and aimed to determine whether certain rTMS parameters, such as cortical target, may be associated with higher treatment effectiveness. After conducting a systematic literature review for RCTs on rTMS for OCD through to 1 December 2016 using MEDLINE, PubMed, Web of Science, PsycINFO, Google, and Google Scholar, we performed a random-effects meta-analysis with the outcome measure as pre-post changes in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To determine whether rTMS parameters may have influenced treatment effectiveness, studies were further analysed according to cortical target, stimulation frequency, and length of follow-up. Data were obtained from 18 RCTs on rTMS in the treatment of OCD. Overall, rTMS yielded a modest effect in reducing Y-BOCS scores with Hedge’s g of 0.79 (95% CI = 0.43–1.15, p < 0.001). Stimulation of the supplementary motor area yielded the greatest reductions in Y-BOCS scores relative to other cortical targets. Subgroup analyses suggested that low frequency rTMS was more effective than high frequency rTMS. The effectiveness of rTMS was also greater at 12 weeks follow-up than at four weeks follow-up. Our meta-analysis implies that low frequency rTMS applied over the supplementary motor area may offer the greatest effectiveness in the treatment of OCD. The therapeutic effects of rTMS also appear to persist post-treatment and may offer beneficial long-term effectiveness. With our findings, it is suggested that future large-scale studies focus on the supplementary motor area and include follow-up periods of 12 weeks or more.

Alzheimer’s disease (AD), is characterized by its progressive feature and loss of cognitive functions, is common among dementia types. There is no curative treatment of the disease today. In recent years, transcranial magnetic stimulation (TMS) techniques together with drug therapy have been explored by experts considering that they will produce beneficial results. Repetetive TMS (rTMS) can modulate cortical excitability and prevent long-term neuroplastic changes. The aim of this study is an updated and comprehensive systematic review of studies using TMS/rTMS in AD patients. Our study was designed as a systematic review prepared according to the PRISMA guideline. In this study, English and Turkish AD-TMS articles that entered the literature published between 2002 and 2017 were included. Randomized and non-randomized controlled clinical studies on humans evaluating the effectiveness of rTMS applications at different concentrations, durations and different regions in AD have been reviewed. The databases we used were Pubmed®, MEDLINE®, Webofscience®, EMBASE®, Türkiye Atif Dizini®. Keywords were “TMS, rTMS, Alzheimers Disease” used in our search, 116 artticles complied with the determined protocol were identified and 14 were included in our study. The studies presented in this review, show the therapeutic potential of rTMS in AD patients. Benefits of rTMS were to communicate with patients and especially caregivers in their daily activities, thereby improving their QoL. The possibility of using TMS to increase neuroplasticity is promising not only to improve our understanding of brain plasticity mechanisms, but also to design new neurorehabilitation strategies.

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are prevalent comorbidities related to a greater likelihood of poor treatment outcomes and prolonged treatment for Reward Deficiency Syndrome (RDS) behaviors. The current exploratory case study of a small cohort (n=3; f=2 m=1) used novel neurotechnology to treat co-occurring MDD and GAD with a multifaceted intervention that combines the novel bio-resonance neurotechnology (BRNT) referred to as NuCalm , to restore autonomic nervous system balance and dual hemispheric repetitive transcranial magnetic stimulation (rTMS) of the ipsilateral Dorsal Lateral Prefrontal Cortex (DLPFC) to treat the disrupted structural components of the brain. Neuroacoustic brainwave entrainment, electromagnetic frequency bio-resonance, and light-blocking combine to place patients into a parasympathetic dominant state. The paired -tests indicated a significant decrease in comparing before and after the intervention. The Patient Health Questionnaire PHQ-9 scores from the first to the last time-point (mean difference = 20, t(2) = 6.55, p = 0.0226), with a 95% confidence interval of mean difference ranging from 6.86 to 33.14. Similarly, there was a significant decrease in General Anxiety Disorder GAD-7 questionnaire scores from the first to the last time point (mean difference = 18.67, t(2) = 12.85, p = 0.0060), with a 95% confidence interval of the mean difference ranging from 12.42 to 24.92. After applying the Bonferroni correction, the corrected p-values for PHQ-9 and GAD-7 are 0.0452 and 0.0120, respectively. Cohen's d standardized effect size indicated that the main effect size was 5.47 and 13.8 times the noise (variability), respectively, for the initial versus final PHQ-9 and GAD-7. Further, more extensive, much larger sham-controlled and blinded studies are required to confirm these encouraging results and explore this multifaceted intervention.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and accounts for most cases of dementia. The prevalence of AD has increased in the current rapidly aging society and contributes to a heavy burden on families and society. Despite the profound impact of AD, current treatments are unable to achieve satisfactory therapeutic effects or stop the progression of the disease. Finding novel treatments for AD has become urgent. In this paper, we reviewed novel therapeutic approaches in five categories: anti-amyloid therapy, anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, and brain stimulation. The trend of therapeutic development is shifting from a single pathological target to a more complex mechanism, such as the neuroinflammatory and neurodegenerative processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), also have the potential for clinical application. In the future, it is possible for physicians to choose appropriate interventions individually on the basis of precision medicine.

Background. We investigated whether transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (S1) and sensory stimulation (SS) could promote upper limb recovery in participants with subacute stroke. Methods. Participants were randomized into four groups: rTMS/Sham SS, Sham rTMS/SS, rTMS/SS, and control group (Sham rTMS/Sham SS). Participants underwent ten sessions of sham or active rTMS over S1 (10 Hz, 1,500 pulses, 120% of resting motor threshold, 20 min), followed by sham or active SS. The SS involved active sensory training (exploring features of objects and graphesthesia, proprioception exercises), mirror therapy, and Transcutaneous electrical nerve stimulation (TENS) in the region of the median nerve in the wrist (he stimulation intensity was determined as the minimum intensity at which the participants reported paresthesia), five electrical pulses of 1 ms duration each at 10 Hz were delivered every second over 45 min. Sham stimulations occurred as follows Sham rTMS: coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation. The Sham SS received therapy in the unaffected upper limb, did not use the mirror and also received TENS stimulation for only 60 seconds. The primary outcome was the Body Structure/Function: Fugl-Meyer Assessment (FMA) and Nottingham Sensory Assessment (NSA); the secondary outcome was the Activity/Participation domains, assessed with Box and Block Test, Motor Activity Log scale, Jebsen-Taylor Test, and Functional Independence Measure. Results. Forty participants with stroke ischemic (n=38) and hemorrhagic (n=2), men (n=19) and women (n=21), in the subacute stage (10.6±6 weeks) had a mean age of 62.2±9.6 years, were equally divided into four groups (10 participants in each group). Significant somatosensory improvements were found in participants receiving active rTMS and active SS, compared with those in the control group (sham rTMS with sham SS). Motor function improved only in participants who received active rTMS, with greater effects when active rTMS was combined with active SS. Conclusion. The combined use of SS with rTMS over S1 represents a more effective therapy for increasing sensory and motor recovery, as well as functional independence, in participants with subacute stroke

Repetitive transcranial magnetic stimulation (rTMS) has been used in the clinical treatment of Parkinson's disease (PD). Most of rTMS studies on PD used high‐frequency stimulation; however, excessive nonvoluntary movement may represent abnormally cortical excitability, which is likely to be suppressed by low‐frequency rTMS. Decreased neural activity in the basal ganglia on functional magnetic resonance imaging (fMRI) is a characteristic of PD. In the present study, we found that low‐frequency (1 Hz) rTMS targeting individual finger‐tapping activation elevated the amplitude of local neural activity (percentage amplitude fluctuation, PerAF) in the putamen as well as the functional connectivity (FC) of the stimulation target and basal ganglia in healthy participants. These results provide evidence for our hypothesis that low‐frequency rTMS over the individual task activation site can modulate deep brain functions, and that FC might serve as a bridge transmitting the impact of rTMS to the deep brain regions. It suggested that a precisely localized individual task activation site can act as a target for low‐frequency rTMS when it is used as a therapeutic tool for PD. A “Steady‐state” paradigm of finger‐tapping task detected that self‐initiated finger‐tapping was more intensively associated with the motor‐related brain area than visual‐guided. Low‐frequency rTMS targeting individual task peak activation could precisely elevated the local neural activity in the putamen. The basal ganglia neural activity may be sensitive to low‐frequency rTMS and the excessive nonvoluntary movement of PD is likely to be suppressed by low‐frequency rTMS rather than high frequency.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neurostimulation technique receiving increasing attention in the treatment of different psychiatric disorders. Evidence for rTMS use in obsessive-compulsive disorder (OCD) is accumulating and informing further developments in the neurostimulation field, the latest being deep transcranial magnetic stimulation (dTMS). dTMS allows direct stimulation of deeper subcortical structures and larger brain volume than conventional rTMS. Underlying neurobiological mechanisms related to transcranial magnetic stimulation are still under evaluation, but appear to offer a novel \"third\" way of addressing symptoms via localized electrical stimulation compared to pharmacotherapy and psychotherapy approaches. This systematic review focuses on the effects of rTMS and dTMS stimulation on different brain targets in OCD. Brain areas included are the dorsolateral prefrontal cortex, supplementary motor area, orbitofrontal cortex/medial prefrontal cortex, and anterior cingulate cortex (ACC). Improved understanding of the therapeutic effects of rTMS in OCD will support fine-tuning of the method and help determine how we can best optimize the approach via rTMS or dTMS to achieve clinically relevant results.

Introduction: High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse durations. Objectives: To investigate the influence of pulse duration, direction, and amplitude in correlation to induced depolarization on the excitatory plastic aftereffects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) using bidirectional cTMS pulses. Methods: We stimulated the hand motor cortex with 5 Hz rTMS applying 1,200 bidirectional pulses with the main component durations of 80, 100, and 120 μs using a controllable pulse stimulator TMS (cTMS). Fourteen healthy subjects were investigated in nine sessions with 80% resting motor threshold (RMT) for posterior-anterior (PA) and 80 and 90% RMT anterior-posterior (AP) induced current direction. We used a model approximating neuronal membranes as a linear first order low-pass filter to estimate the strength–duration time constant and to simulate the membrane polarization produced by each waveform. Results: PA and AP 5 Hz rTMS at 80% RMT produced no significant excitation. An exploratory analysis indicated that 90% RMT AP stimulation with 100 and 120 μs pulses but not 80 μs pulses led to significant excitation. We found a positive correlation between the plastic outcome of each session and the simulated peak neural membrane depolarization for time constants >100 μs. This correlation was strongest for neural elements that are depolarized by the main phase of the AP pulse, suggesting the effects were dependent on pulse direction. Conclusions: Among the tested conditions, only 5 Hz rTMS with higher intensity and wider pulses appeared to produce excitatory aftereffects. This correlated with the greater depolarization of neural elements with time constants slower than the directly activated neural elements responsible for producing the motor output (e.g., somatic or dendritic membrane). Significance: Higher intensities and wider pulses seem to be more efficient in inducing excitation. If confirmed, this observation could lead to better results in future clinical studies performed with wider pulses.