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Background: Abnormalities in cortical excitability and plasticity have been considered to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) can provide a direct evaluation of cortical responses to TMS. Here, we employed TMS-EEG to investigate cortical responses to orbitofrontal cortex (OFC) stimulation in schizophrenia., Methods: In total, we recruited 92 drug-naïve patients with first-episode schizophrenia and 51 age- and sex-matched healthy individuals. For each participant, one session of 1-Hz repetitive TMS (rTMS) was delivered to the right OFC, and TMS-EEG data were obtained to explore the change in cortical-evoked activities before and immediately after rTMS during the eyes-closed state. The MATRICS Consensus Cognitive Battery was used to assess neurocognitive performance., Results: The cortical responses indexed by global mean field amplitudes (i.e., P30, N45, and P60) were larger in patients with schizophrenia than in healthy control participants at baseline. Furthermore, after one session of 1-Hz rTMS over the right OFC, the N100 amplitude was significantly reduced in the healthy control group but not in the schizophrenia group. In the healthy control participants, there was a significant correlation between modulation of P60 amplitude by rTMS and working memory; however, this correlation was absent in patients with schizophrenia., Conclusions: Aberrant global cortical responses following right OFC stimulation were found in patients with drug-naïve first-episode schizophrenia, supporting its significance in the primary pathophysiology of schizophrenia., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Negative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT)., Method: This is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex., Results: Two distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η 2  = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group., Conclusions: The 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Intermittent theta burst stimulation (iTBS) is based on the phase-amplitude coupling (PAC) pattern. We aimed to investigate the effect of iTBS on PAC in resting electroencephalography (EEG), which may provide insight into the underlying mechanism., Methods: Twenty-one healthy volunteers were recruited and received both active and sham neuroimaging-guided iTBS on two separate days, which was precisely delivered to the right superior temporal gyrus. On each experimental day, resting EEG was recorded before and after stimulation for each participant. PACs across electrodes and frequency bands were calculated and compared to investigate the effect of iTBS., Results: Theta (4-6 Hz) -low gamma (45-55 Hz) PAC over the stimulation site had a significant interaction effect, which increased after the active iTBS but did not differ after the sham iTBS. No significant interaction effect occurred in other cross-frequency couplings such as delta-low gamma, alpha-low gamma, delta-high gamma, theta-high gamma, or alpha-high gamma PAC in the region of interest., Conclusion: iTBS selectively modulated theta-low gamma PAC at the stimulation area, which exhibited both region- and frequency- specificity. This suggests that PAC may be a bridge connecting external neuromodulation to internal neuroplasticity., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is a well-established, safe, and effective brain stimulation technique for depression; however, uniform parameters have not been used in clinical practice. The aim of this study was to identify the parameters that affect rTMS effectiveness and ascertain the range in which that parameter has optimal efficacy. A meta-analysis of sham-controlled trials using rTMS delivered over the left dorsolateral prefrontal cortex (DLPFC) in depression was conducted. In the meta-regression and subgroup analyses, all rTMS stimulation parameters were extracted and their association with efficacy was investigated. Of the 17,800 references, 52 sham-controlled trials were included. Compared to sham controls, our results demonstrated a significant improvement in depressive symptoms at the end of treatment. According to the results of meta-regression, the number of pulses and sessions per day correlated with rTMS efficacy; however, the positioning method, stimulation intensity, frequency, number of treatment days, and total pulses did not. Furthermore, subgroup analysis revealed that the efficacy was correspondingly better in the group with higher daily pulses. In clinical practice, increasing the number of daily pulses and sessions may improve the effectiveness of rTMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Positive reappraisal aims to reinterpret negative situations in a more positive light. Single-pulse transcranial magnetic stimulation (TMS) over the left ventrolateral prefrontal cortex (VLPFC) during positive reappraisal was suggested to improve emotion regulation capacity. However, it remains unclear whether the improvement of the capacity of emotion regulation was caused by the alterations of neural activity with TMS perturbation over the left VLPFC during positive reappraisal., Methods: Single-pulse TMS was delivered among fifteen participants who engaged in positive reappraisal experiments with concurrent electroencephalogram (EEG) recordings. Participants repeated positive reappraisal experiments at three different stimulation settings: no stimulation, TMS pulses over the left VLPFC at 300 ms post-stimulus as the targeted stimulation and over the vertex as the control stimulation., Results: TMS pulses over the left VLPFC at 300 ms post-stimuli increased late positive potential (LPP) amplitudes (300-800 ms) within the central-parietal and right prefrontal regions in response to the reappraisal stimuli compared with the negative stimuli. Moreover, changes in neural activity within the frontoparietal network contributed to the modulated LPP amplitudes of the reappraisal stimuli with the targeted stimulation. Importantly, the central-parietal LPP amplitudes of the reappraisal stimuli with the targeted stimulation was not only correlated with but also could predict the valence ratings using positive reappraisal., Conclusion: Our study demonstrated a causal role of the left VLPFC in positive reappraisal, and provided a neural indicator to indicate the degree to which single-pulse TMS modulated the emotional experience using positive reappraisal. It shows promise to apply in future closed-loop neuromodulation., (Copyright © 2021. Published by Elsevier B.V.)

Background: Repetitive transcranial magnetic stimulation (rTMS) offers promise for the treatment of depression, yet its potential impact on suicidal ideation (SI), particularly in adolescents, has not been well studied. This study aimed to investigate the efficacy of add-on rTMS for reducing SI in a large clinical sample experiencing an acute phase of depression., Methods: This study included 146 patients with a score of ≥14 on the 17-item Hamilton Rating Scale for Depression (HAMD). Among them, 97 had a HAMD-SI (3-item) score of 1 or greater and were pooled into the analysis. Symptoms of depression and SI were measured using the HAMD total score and HAMD-SI score. Comparisons of clinical improvement for both SI and rates of remission were made between adolescent (n = 29) and adult patients (n = 68), as well as between high-frequency (HF) rTMS on the left dorsolateral prefrontal cortex (DLPFC) (80 trains, 30 pulses per train, 12 s intertrain interval, 2400 pulses per session) and low-frequency (LF) rTMS on the right DLPFC protocol (2 trains, 700 pulses per train, 1 s intertrain-interval, 1400 pulses per session), power (intensity) level of 120% of motor threshold (MT), and 5 sessions per week for 2 weeks., Results: Add-on rTMS treatment showed significant clinical improvement in SI, and was also well tolerated, with no adverse events reported. The SI improvements and remission rates were more significant in adolescents treated with the HF left DLPFC rTMS protocol, compared with adults treated with the LF right DLPFC rTMS protocol (remission rates: adolescent with LF right DLPFC, 50%; adolescent with HF left DLPFC, 94%; adult with LF right DLPFC, 65%; adult with HF left DLPFC, 57%). A positive association between improvement in the HAMD total score and HAMD-SI score was found in adults, but not in adolescents., Conclusions: Add-on rTMS treatment for SI associated with depression is promising with respect to safety and feasibility. Our preliminary evidence supports an extension of the application of rTMS to adolescent patients with SI during the acute phase of depression, in addition to its use in adult treatment-resistant depression., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Negative symptoms are the major challenge in clinical management of schizophrenia. Dorsomedial prefrontal cortex (DMPFC) has been suggested to be highly involved in the mechanisms of negative symptoms of schizophrenia. However, the effect of repetitive Transcranial Magnetic Stimulation (rTMS) over DMPFC has not yet been well studied. In this double-blind, randomized controlled rTMS clinical trial, thirty-three participants (17 in active group and 16 in sham group) were enrolled. This study includes the rTMS treatment phase (lasts for 4 weeks) and a subsequently naturalistic follow-up phase (lasts for another 4 weeks). Schizophrenia patients with prominently negative symptoms were randomly assigned to receive 10 Hz or sham rTMS intervention. The score change in Scale of Negative Symptoms (SANS) was defined as the primary outcome measure. There was a significant decrease in negative symptoms, especially affective flattening and anhedonia in schizophrenia patients after DMPFC-rTMS intervention. Moreover, the negative symptoms improvement could maintain at least another 4 weeks. In addition, no memory impairment or serious adverse reaction of rTMS emerged. Our results suggest that high frequency rTMS over DMPF may represent a safe and effective treatment for negative symptoms in patients with schizophrenia., (Copyright © 2021. Published by Elsevier B.V.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant treatment for depression. Many patients with depression have comorbid anxiety symptoms. However, previous rTMS studies have focused on patients with depression, and often excluded comorbid anxiety. This real-world study aimed to investigate the comparative efficacy of add-on rTMS in treating the somatic and psychic anxiety symptoms of depression comorbid with anxiety in adolescents, adults and elderly patients., Methods: This study included 147 depression patients with anxiety symptoms who were treated with at least 10 sessions of rTMS. The symptoms of anxiety and depression were assessed with the Hamilton Rating Scale for Anxiety (HAMA) and the Hamilton Rating Scale for Depression (HAMD) at baseline and after 2 and 4 weeks of treatment. This was done to compare the improvement degree of add-on rTMS on somatic and psychic anxiety symptoms in adolescents, adults and elderly patients respectively., Results: Both somatic and psychic anxiety symptoms were significantly improved after the add-on rTMS in adolescents, adults and elderly patients. The improvement of somatic anxiety was better than that of psychic anxiety after rTMS treatment in elderly patients (t 2w =3.895, P<0.001; t 4w =2.823, P = 0.008)., Limitation: The overall sample was mostly composed of elderly patients, while adolescents and adult patients were fewer., Conclusions: The add-on rTMS treatment can improve somatic anxiety better than psychic anxiety in depression with anxiety symptoms, especially in elderly patients., (Copyright © 2020. Published by Elsevier B.V.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is now an established, safe, and effective treatment for adults with depression. However, specific research in rTMS for use in elderly patients with acute depression is scarce., Objective: The aim of the present study was to investigate the efficacy of add-on rTMS in a clinical sample of older adults experiencing an acute phase of depression., Method: This study examined 114 patients (54 elderly [aged ≥60] and 60 adults [aged 18-59]) with acute depression who were drug free at baseline. They were treated with at least 10 sessions of rTMS for 4 weeks along with 1 antidepressant. Symptoms of depression were measured using the Hamilton Rating Scale for Depression at baseline and after 2 and 4 weeks of treatment. Clinical improvement and rates of response and remission were compared across groups., Results: Significant improvement was noted after 2 and 4 weeks of treatment in both adult and elderly groups. Higher remission rates were found in adult patients but with no differences in response. The stimulation intensity and course of illness were significant predictors of remission after 4 weeks of rTMS treatment in the elderly., Conclusions: The add-on rTMS treatment for elderly depression patients is promising with respect to safety and feasibility. This preliminary evidence supports the application of rTMS to this group during acute episodes.

Speed of Processing (SoP) represents a fundamental limiting step in cognitive performance which may underlie General Intelligence. The measure of SoP is particularly sensitive to aging, neurological or cognitive diseases, and has become a benchmark for diagnosis, cognitive remediation, and enhancement. Neural efficiency of the Dorsolateral Prefrontal Cortex (DLPFC) is proposed to account for individual differences in SoP. However, the mechanisms by which DLPFC efficiency is shaped by training and whether it can be enhanced remain elusive. To address this, we monitored the brain activity of sixteen healthy participants using functional Near Infrared Spectroscopy (fNIRS) while practicing a common SoP task (Symbol Digit Substitution Task) across 4 sessions. Furthermore, in each session, participants received counterbalanced excitatory repetitive transcranial magnetic stimulation (rTMS) during mid-session breaks. Results indicate a significant involvement of the left-DLPFC in SoP, whose neural efficiency is consistently increased through task practice. Active neurostimulation, but not Sham, significantly enhanced the neural efficiency. These findings suggest a common mechanism by which neurostimulation may aid to accelerate learning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is considered as an effective treatment for adults with major depressive disorder. However, it remains unknown whether rTMS has comparable or better efficacy in adolescents., Objective: The current naturalistic study aimed to investigate the efficacy and clinical outcome of add-on rTMS in a large sample of adolescent patients compared to adult patients., Methods: This study included 117 patients (42 adolescents vs. 75 adults) with mood or anxiety disorders who were treated with at least 10 sessions of rTMS. rTMS was applied over the left dorsolateral prefrontal cortex (10 Hz). Symptoms of depression and anxiety were measured using the Hamilton Rating Scale for Depression (HAMD) and the Hamilton Rating Scale for Anxiety (HAMA) respectively, at baseline and after 2 and 4 weeks of follow-up. Comparisons of clinical improvement and rates of response/remission were made across age groups., Major Findings and Conclusions: All the age groups showed significant improvements in clinical symptoms. No safety or tolerability concerns were identified. Symptomatic improvements and response/remission rates were more significant in adolescent patients than in adults. Decrease in HAMD and HAMA scores after 2 weeks and 4 weeks of rTMS treatment were positively correlated in adolescents, but not in adults. General linear model repeated measures demonstrated significant effect of time × age group interaction on the HAMD score, in response to 10 sessions of rTMS. Add-on rTMS is feasible, tolerable, effective and more applicable to adolescents with mood or anxiety disorders. However, double-blinded and sham-controlled trials are needed for validating this conclusion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Mismatch negativity (MMN) is a typical event-related potential component reflecting pre-attentive processing. MMN impairment, especially reduced duration-related MMN (dMMN), has been suggested as a potential predictive biomarker for the onset of schizophrenia., Objective: This study attempts to manipulate specific MMN activities using advanced neuroimaging-guided intermittent theta-burst stimulations (iTBS), which will be helpful to uncover the sources of MMN generation and contribute to the development of new clinical treatments., Methods: Twenty-four healthy volunteers were recruited and participated two-session modulations consisting of active and sham iTBS. ITBS was precisely delivered over individual right posterior superior temporal cortex (pSTG). Before and after each iTBS session, two MMN components evoked by duration and frequency deviants were quantified respectively., Results: A significant interaction of time and iTBS was observed on dMMN amplitudes, but not frequency-related MMN amplitudes. dMMN only decreased after active precise iTBS intervention, but did not after sham iTBS. The post effect of iTBS on dMMN was found in 16 of 20 subjects, suggesting a robust effect even at individual level. Furthermore, sLORETA analysis showed that the lateralization of STG activation was reversed after the active iTBS., Conclusions: We applied a precise strategy for neuroimaging-guided iTBS modulation over the right pSTG, which is promising in selectively modulating MMN for specific deviants., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Prefrontal cortex (PFC) plays an important role in emotional processing and therefore is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) in clinical trials, especially in the treatment of emotional disorders. As an approach to enhance the effectiveness of rTMS, continuous theta burst stimulation (cTBS) has been demonstrated to be efficient and safe. However, it is unclear how cTBS affects brain processes related to emotion. In particular, psychophysiological studies on the underlying neural mechanisms are sparse. In the current study, we investigated how the cTBS influences emotional processing when applied over the right PFC. Participants performed an emotion recognition Go/NoGo task, which asked them to select a GO response to either happy or fearful faces after the cTBS or after sham stimulation, while 64-channel electroencephalogram (EEG) was recorded. EEG oscillation was examined using event-related spectral perturbation (ERSP) in a time-interval between 170 and 310ms after face stimuli onset. In the sham group, we found a significant difference in the alpha band between response to happy and fearful stimuli but that effect did not exist in the cTBS group. The alpha band activity at the scalp was reduced suggesting the excitatory effect at the brain level. The beta and gamma band activity was not sensitive to cTBS intervention. The results of the current study demonstrate that cTBS does affect emotion processing and the effect is reflected in changes in EEG oscillations in the alpha band specifically. The results confirm the role of prefrontal cortex in emotion processing. We also suggest that this pattern of cTBS results elucidates mechanisms by which mood improvement in depressive disorders is achieved using cTBS intervention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

With the ability to modulate cortical activity, repetitive transcranial magnetic stimulation (rTMS) is becoming increasingly important in clinical applications for psychiatric disorders. Previous studies have demonstrated its promising efficacy in depression and schizophrenia, and emerging evidence has also been found in patients with anxiety disorder, obsessive-compulsive disorder, and substance or food craving. However, the overall literature features some conflicting results, varied quality of studies, and a lack of consensus on optimal rTMS parameters. Besides, the efficacy of rTMS in patients with medication-resistant symptoms has drawn most attention from clinicians. Here we review multi-site studies and double-blind randomized controlled trials (RCTs) in single sites, as well as meta-analyses of RCTs in the last three years, in order to update evidence on efficacy and the optimal protocol of rTMS in psychiatric disorders, especially for medication-resistant symptoms.

Objective: We aimed to investigate the influence of high frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on excitability of the masseter inhibitory reflex (MIR) in healthy subjects. Our goal in conducting this study was to obtain a better understanding of the subcortical and cortical networks related to the excitability of the central masticatory pathway., Methods: Twenty healthy volunteers participated in this study. MIRs were evaluated both before and after high frequency rTMS to elicit motor evoked potentials (MEPs) using single- and double-shock techniques over the motor cortex. During measurements, the latency and duration of silent periods (SPs) with single magnetic stimulation, and the recovery of SP2 with the double-shock technique, were recorded in basal conditions and immediately after high frequency rTMS. The "real" rTMS condition consisted of 20 stimulus trains delivered at 10Hz with a 5-s stimulation duration and an intensity of 70% of the active motor threshold (AMT) over the right optimal motor spot for the masseter muscle., Results: were also compared to those obtained after "sham" rTMS 1 week later RESULTS: Using the double-shock technique, SP2 recovery time was significantly shorter after high frequency rTMS compared to the basal condition (from 100 to 400ms; p<0.001), while at ISIs of 500 and 600ms, no significant effect was observed (p=0.084, p=0.948). There was also no significant change in the SP latency or duration between groups (p>0.05)., Conclusions: High frequency, sub-threshold rTMS of the motor cortex had a facilitative after-effect on the excitability of the MIR. This effect was likely mediated through increased cortical drive to brainstem reflex pathways, which would ultimately accelerate MIR recovery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation and modulation electrophysiological technique, it can change cortical excitability of target brain region, modulate neuron plasticity and brain connections. Previous researches indicated that rTMS could reduce cue-induced craving in drug addiction., Objective: In this study, we employed real and sham rTMS of the left dorsolateral prefrontal cortex (DLPFC) to test whether it could reduce cue-induced craving for methamphetamine (MA) and influence cognitive function in a randomised clinical trial., Methods: Thirty MA-addicted patients were randomized to receive 5 sessions of 8min sham or 10Hz rTMS to the left DLPFC. Subjects rated their craving at baseline, after exposed to MA-associated cues and after rTMS sessions., Results: Real rTMS over the left DLPFC reduced craving significantly after 5 sessions of rTMS as compared to sham stimulation. Furthermore, real rTMS improved verbal learning and memory and social cognition in MA-addicted patients., Conclusions: The present study suggests that 10Hz rTMS of the left DLPFC may reduce craving and have no negative effects on cognitive function in MA-addicted patients, supporting the safety of rTMS in treating MA addiction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Panic disorder (PD) is a common type of anxiety disorder, characterized by unexpected and repeated panic attacks or fear of future panic attacks, or both. Individuals with PD are often resistant to pharmacological or psychological treatments and this can lead to the disorder becoming a chronic and disabling illness. Repetitive transcranial magnetic stimulation (rTMS) can deliver sustained and spatially selective current to suppress or induce cortical excitability, and its therapeutic effect on pathological neuronal activity in people with PD has already been examined in case studies and clinical trials. However, a systematic review is necessary to assess the efficacy and safety of rTMS for PD., Objectives: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) for panic disorder (PD) in adults aged 18 to 65 years, either as a monotherapy or as an augmentation strategy., Search Methods: An electronic search of the Cochrane Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR) was conducted to 19 February 2014. The CCDANCTR includes reports of relevant randomised controlled trials (RCTs) from MEDLINE (1950 to date), EMBASE (1974 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL) (all years). Additional searches were conducted in Psyndex and the main Chinese medical databases., Selection Criteria: RCTs or quasi-randomised trials evaluating rTMS for PD in people aged between 18 and 65 years, either as a monotherapy or as an augmentation strategy., Data Collection and Analysis: Two review authors independently selected studies and extracted data and verified the data by cross-checking. Disagreements were resolved by discussion. For binary data, we calculated fixed-effect model risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we calculated fixed-effect model standardized mean difference (SMD) and its 95% CI., Main Results: Two RCTs (n = 40) were included in this review. The included trials compared rTMS with sham rTMS; no trials comparing rTMS with active treatments (electroconvulsive therapy (ECT), pharmacotherapy, psychotherapy) met our inclusion criteria. Both included studies used 1 Hz rTMS over the right dorso-lateral prefrontal cortex (DLPFC) for two or four weeks as an augmentation treatment for PD. However, in both studies the data for the primary outcome, panic symptoms as measured by the Panic Disorder Severity Scale (PDSS), were skewed and could not be pooled for a quantitative analysis. For this primary outcome one trial with 25 participants reported a superior effect of rTMS in reducing panic symptoms compared with sham rTMS (t = 3.04, df = 16.57, P = 0.007), but this trial had a 16% dropout rate and so was deemed as having a high risk of attrition bias. The other trial found that all 15 participants exhibited a reduction in panic symptoms but there was no significant difference between rTMS and sham rTMS (Mann Whitney U test, P > 0.05). Regarding the acceptability of rTMS, no significant difference was found between rTMS and sham rTMS in dropout rates or in reports of side effects. The quality of evidence contributing to this review was assessed as very low. Assessments of the risk of bias for the two studies were hampered by the lack of information provided in the reports, especially on methods of sequence generation and whether allocation concealment had been applied. Of the remaining sources of bias, we considered one of the studies to have been at risk of attrition bias., Authors' Conclusions: Only two RCTs of rTMS were available and their sample sizes were small. The available data were insufficient for us to draw any conclusions about the efficacy of rTMS for PD. Further trials with large sample sizes and adequate methodology are needed to confirm the effectiveness of rTMS for PD.

Electroconvulsive therapy (ECT) is the most effective treatment of depression. During the last decades repetitive transcranial magnetic stimulation (rTMS), an alternative method using electric stimulation of the brain, has revealed possible alternative to ECT in the treatment of depression. There are some clinical trials comparing their efficacies and safeties but without clear conclusions, mainly due to their small sample sizes. In the present study, a meta-analysis had been carried out to gain statistical power. Outcomes were response, remission, acceptability and cognitive effects in depression. Following a comprehensive literature search that included both English and Chinese language databases, we identified all randomized controlled trials that directly compared rTMS and ECT for major depression. 10 articles (9 trials) with a total of 425 patients were identified. Methodological quality, heterogeneity, sensitivity and publication bias were systematically evaluated. ECT was superior to high frequency rTMS in terms of response (64.4% vs. 48.7%, RR = 1.41, p = 0.03), remission (52.9% vs. 33.6%, RR = 1.38, p = 0.006) while discontinuation was not significantly different between the two treatments (8.3% vs. 9.4%, RR = 1.11, p = 0.80). According to the subgroup analysis, the superiority of ECT was more apparent in those with psychotic depression, while high frequency rTMS was as effective as ECT in those with non-psychotic depression. The same results were obtained in the comparison of ECT with low frequency rTMS. ECT had a non-significant advantage over high frequency rTMS on the overall improvement in HAMD scores (p = 0.11). There was insufficient data on medium or long term efficacy. Both rTMS and ECT were well tolerated with only minor side effects reported. Results based on 3 studies suggested that specific cognitive domains such as visual memory and verbal fluency were more impaired in patients receiving ECT. In conclusion, ECT seemed more effective than and at least as acceptable as rTMS in the short term, especially in the presence of psychotic depression. This review identified the lack of good quality trials comparing the long-term outcome and cognitive effects of rTMS and ECT, especially using approaches to optimize stimulus delivery and reduce clinical heterogeneity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Hypothesis Cognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year. Study Design Sixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis. Study Results We observed significant VSL improvements in the active TMS subgroup (Cohen's d = 0.71, P <.001) but not in the sham TMS subgroup (Cohen's d = 0.07, P =.70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ 2 = 4.45, P =.03). Conclusions Our findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up. [ABSTRACT FROM AUTHOR]

Metacognition refers to the ability to be aware of one's own cognition. Ample evidence indicates that metacognition in the human primate is highly dissociable from cognition, specialized across domains, and subserved by distinct neural substrates. However, these aspects remain relatively understudied in macaque monkeys. In the present study, we investigated the functionality of macaque metacognition by combining a confidence proxy, hierarchical Bayesian meta-d′ computational modelling, and a single-pulse transcranial magnetic stimulation technique. We found that Brodmann area 46d (BA46d) played a critical role in supporting metacognition independent of task performance; we also found that the critical role of this region in meta-calculation was time-sensitive. Additionally, we report that macaque metacognition is highly domain-specific with respect to memory and perception decisions. These findings carry implications for our understanding of metacognitive introspection within the primate lineage. Use of transcranial magnetic stimulation in macaques reveals a potential role for Brodmann area 46d (BA46d) in supporting metacognition, or the ability to be aware of one's own thoughts. [ABSTRACT FROM AUTHOR]

Background: Orthodontic treatment is a common clinical method of malocclusion. Studies have found that neurons in the sensorimotor cortex of the brain undergo adaptive remodeling in response to changes in oral behavior or occlusion. Objective: To explore whether orthodontic treatment could be sufficient to cause neuroplastic changes in the corticomotor excitability of the masseter muscle. Methods: Fifteen Angle Class II malocclusion patients who were receiving orthodontic treatment participated in the study. Cortical excitability was assessed by electromyographic activity changes evoked by transcranial magnetic stimulation. Four orthodontic time points were recorded, including baseline, day 1, day 7, and day 30. Motor evoked potentials (MEPs) were recorded in the masseter muscle and the first dorsal interosseous muscle (FDI) serving as a control. The data were analysed by stimulus–response curves and corticomotor mapping. Statistical analyses involved repeated measures analysis of variance, two‐way ANOVA, and Tukey's post hoc tests. Results: Motor evoked potentials (MEPs) of the masseter muscle were significantly decreased during orthodontic treatment compared with those of the baseline (p <.001). MEPs of the masseter muscle were dependent on session and stimulus intensity (p <.001), whereas MEPs of FDI were only dependent on stimulus intensity (p =.091). Finally, Tukey's post hoc tests demonstrated that MEPs of the masseter muscle on days 1 and 7, with 70%–90% stimulus intensities, were higher than those of baseline values (p <.001). Conclusions: The present study suggested that orthodontic treatment can lead to neuroplastic changes in the corticomotor control of the masseter muscle, which may add to our understanding of the adaptive response of subjects to changes of oral environment during the orthodontic treatment. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is an early stage of Alzheimer's disease. Repetitive transcranial magnetic stimulation (rTMS) has been widely employed in MCI research. However, there is no reliable systematic evidence regarding the effects of rTMS on MCI. The aim of this review was to evaluate the efficacy and safety of rTMS in the treatment of MCI. Methods: A comprehensive literature search of nine electronic databases was performed to identify articles published in English or Chinese before June 20, 2019. The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. The meta-analysis was performed using the RevMan 5.3 software. We used the GRADE approach to rate the quality of the evidence. Results: Nine studies comprising 369 patients were included. The meta-analysis showed that rTMS may significantly improve global cognitive function (standardized mean difference [SMD] 2.09, 95% confidence interval [CI] 0.94 to 3.24, p = 0.0004, seven studies, n = 296; low-quality evidence) and memory (SMD 0.44, 95% CI 0.16 to 0.72, p = 0.002, six studies, n = 204; moderate-quality evidence). However, there was no significant improvement in executive function and attention (p > 0.05). Subgroup analyses revealed the following: (1) rTMS targeting the left hemisphere significantly enhanced global cognitive function, while rTMS targeting the bilateral hemispheres significantly enhanced global cognitive function and memory; (2) high-frequency rTMS significantly enhanced global cognitive function and memory; and (3) a high number of treatments ≥20 times could improve global cognitive function and memory. There was no significant difference in dropout rate (p > 0.05) between the rTMS and control groups. However, patients who received rTMS had a higher rate of mild adverse effects (risk ratio 2.03, 95% CI 1.16 to 3.52, p = 0.01, seven studies, n = 317; moderate-quality evidence). Conclusions: rTMS appears to improve global cognitive function and memory in patients with MCI and may have good acceptability and mild adverse effects. Nevertheless, these results should be interpreted cautiously due to the relatively small number of trials, particularly for low-frequency rTMS. [ABSTRACT FROM AUTHOR]

Purpose: The utility of transcranial magnetic stimulation (TMS) has been growing rapidly in both neurocognitive studies and clinical applications in decades. However, it remains unclear how the responses of the stimulated site and the site-related functional network to the external TMS manipulation dynamically change over time. Methods: A multi-session combining TMS-fMRI experiment was conducted to explore the spatiotemporal effects of TMS within the fronto-limbic network. Ten healthy volunteers were modulated by intermittent theta-burst stimulation (iTBS) at a precise site within the left dorsolateral prefrontal cortex (DLPFC, MNI coordinate [-44 36 20]), navigated by individual structural MRI image. Three-session resting-state fMRI images were acquired before iTBS (TP1), immediately after iTBS (TP2), and 15 min after iTBS (TP3) for each participant. Seventy-four regions of interests (ROIs) within the fronto-limbic network were chosen including the bilateral superior frontal gyrus (SFG), middle frontal gyrus (MidFG), inferior frontal gyrus (IFG), orbital gyrus (OrG), cingulate gyrus (CG), and subcortical nuclei (hippocampus and amygdala). Regional fractional amplitude of low-frequency fluctuation (fALFF) and ROI-to-ROI functional connectivity (FC) were compared among TP1, TP2, and TP3. Results: The immediate iTBS effect was observed at the stimulated site. FC between the left dorsolateral SFG and left dorsal IFG and between the left rostral IFG and right MidFG increased at TP2 as compared to at TP1 (all FDR- p < 0.05), while FC within the left OrG decreased. The relatively long-term iTBS effect transmitted with decreased FC between the left IFG and right amygdala, increased FC between the left MidFG and left OrG, and decreased FC between bilateral IFG and OrG at TP3 than at TP1 (all FDR- p < 0.05). Meanwhile, mean fALFF values over the left SFG, MidFG, ventral CG, and IFG were significantly increased at TP3 as compared to those at TP2 (all p < 0.05 with Bonferroni correction). Conclusion: By combining TMS and fMRI, it becomes possible to track the spatiotemporal dynamics of TMS after-effects within the fronto-limbic network. Our findings suggested that the iTBS effect dynamically changed over time from the local neural activation at the stimulated site to its connected remote regions within the fronto-limbic network. [ABSTRACT FROM AUTHOR]

aiming Zhuo,1 Yingying Tang,1,2 Zhenhua Song,1 Yingchan Wang,1 Junjie Wang,2 Zhenying Qian,2 Hui Li,2 Qiong Xiang,1 Tianyi Chen,1,3 Zhilei Yang,1,4 Yifeng Xu,1,5 Xiaoduo Fan,6 Jijun Wang,1–2,5 Dengtang Liu1,51First-episode Schizophrenia and Early Psychosis Program, Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 3Shanghai Hong Kou Mental Health Center, Shanghai, People's Republic of China; 4Shanghai Jia Ding Mental Health Center, Division of Psychotic Disorders, Shanghai, People's Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 6Psychotic Disorders Program, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA, USA Purpose: Effective treatment options for negative symptoms and cognitive impairment in patients with schizophrenia are still to be developed. The present study was to examine potential benefits of repetitive transcranial magnetic stimulation (rTMS) to improve negative symptoms and cognition in this patient population. Methods: The study was a 4-week, randomized, double-blind sham-controlled trial. Patients with schizophrenia were treated with adjunctive 20-Hz rTMS for 4 weeks or sham condition to the left dorsolateral prefrontal cortex (DLPFC). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative symptom scale (PANSS) negative subscale at baseline and week 4. Cognitive function was measured using the MATRICS Consensus Cognitive Battery (MCCB) at the same two time points. In addition, possible moderators for rTMS treatment efficacy were explored. Results: Sixty patients (33 in the treatment group, 27 in the sham group) completed the study. There was a significant decrease in negative symptoms after 4-week rTMS treatment as measured by the SANS total score and the PANSS negative symptom subscale score. However, there was no significant improvement in cognition with rTMS treatment. Stepwise multiple linear regression analysis suggested that the baseline severity of positive symptoms may predict poorer improvement in negative symptoms at week 4. Conclusion: Twenty-Hz rTMS stimulation over left DLPFC as an adjunctive treatment might be beneficial in improving negative symptoms of schizophrenia. Future studies with a longer treatment duration and a larger sample size are needed. Clinical trial ID:  NCT01940939. [ABSTRACT FROM AUTHOR]

Background: The capacity for TMS to elicit neural activity and manipulate cortical excitability has created significant expectation regarding its use in both cognitive and clinical neuroscience. However, the absence of an ability to quantify stimulation effects, particularly outside of the motor cortex, has led clinicians and researchers to pair noninvasive brain stimulation with noninvasive neuroimaging techniques. fNIRS, as an optical and wearable neuroimaging technique, is an ideal candidate for integrated use with TMS. Together, TMS+fNIRS may offer a hybrid alternative to "blind" stimulation to assess NIBS in therapy and research. Objective: In this systematic review, the current body of research into the transient and prolonged effects of TMS on fNIRS-based cortical hemodynamic measures while at rest and during tasks are discussed. Additionally, studies investigating the relation of fNIRS to measures of cortical excitability as produced by TMS-evoked Motor-Evoked-Potential (MEP) are evaluated. The aim of this review is to outline the integrated use of TMS+fNIRS and consolidate findings related to use of fNIRS to monitor changes attributed to TMS and the relationship of fNIRS to cortical excitability itself. Methods: Key terms were searched in PubMed and Web-of-Science to identify studies investigating the use of both fNIRS and TMS. Works from Google-Scholar and referenced works in identified papers were also assessed for relevance. All published experimental studies using both fNIRS and TMS techniques in the study methodology were included. Results: A combined literature search of neuroimaging and neurostimulation studies identified 53 papers detailing the joint use of fNIRS and TMS. 22/53 investigated the immediate effects of TMS at rest in the DLPFC and M1 as measured by fNIRS. 21/22 studies reported a significant effect in [HbO] for 40/54 stimulation conditions with 14 resulting an increase and 26 in a decrease. While 15/22 studies also reported [HbR], only 5/37 conditions were significant. Task effects of fNIRS+TMS were detailed in 16 studies, including 10 with clinical populations. Most studies only reported significant changes in [HbO] related measures. Studies comparing fNIRS to changes in MEP-measured cortical excitability suggest that fNIRS measures may be spatially more diffuse but share similar traits. Conclusion: This review summarizes the progress in the development of this emerging hybrid neuroimaging & neurostimulation methodology and its applications. Despite encouraging progress and novel applications, a lack of replicated works, along with highly disparate methodological approaches, highlight the need for further controlled studies. Interpretation of current research directions, technical challenges of TMS+fNIRS, and recommendations regarding future works are discussed. [ABSTRACT FROM AUTHOR]

Objective: Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods: Thirty‐five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video‐polysomnogram monitoring. Transcranial magnetic stimulation motor‐evoked potential (TMS‐MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results: Based on the video and electromyogram observations, a typical cataplectic attack (CA) process is divided into four stages: triggering (CA1), resisting (CA2), atonic (CA3), and recovering stages (CA4). Compared with healthy controls, NT1 patients showed significantly decreased intracortical facilitation during quiet wakefulness. During the laughter stage, both patients and controls showed increased MEP amplitude compared with quiet wakefulness. The MEP amplitude significantly increased even higher in CA1 and 2, and then dramatically decreased in CA3 accompanied with prolonged MEP latency compared with the laughter stage and quiet wakefulness. The MEP amplitude and latency gradually recovered during CA4. Interpretation: This study identifies four stages during cataplectic attack and reveals the existence of a resisting stage that might change the process of cataplexy. The fluctuation of MEP amplitude and MEP latency shows a potential participation of PMC and motor control pathway during cataplexy, and the increased MEP amplitude during CA1 and 2 strongly implies a compensatory mechanism in motor control that may resist or avoid cataplectic attack. [ABSTRACT FROM AUTHOR]

• This is the first study to explore the therapeutic effect of 1 Hz rTMS over right orbitofrontal cortex (OFC) in patients with first-episode schizophrenia. • 1Hz rTMS applied to the right orbitofrontal cortex can improve psychotic symptoms and cognitive deficits in patients with drug-naïve, first-episode schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) has been used in the treatment of patients with schizophrenia. The conventional targets of rTMS treatment are the dorsolateral prefrontal cortex (DLPFC) and temporoparietal cortex (TPC). However, the efficacy of these two treatment strategies was quite heterogeneous. Structural and functional abnormalities of the orbitofrontal cortex (OFC) in schizophrenia are closely related to negative symptoms. We sought to determine whether 1 Hz rTMS over the right OFC is effective in treating patients with first-episode schizophrenia. In this study, eighty-nine patients with drug-naïve, first-episode schizophrenia were randomly divided into the rTMS (n = 47) or sham stimulation (n = 42) groups, with both groups receiving twenty sessions of 1 Hz rTMS treatment. The PANSS was assessed at baseline, day 10, and day 20, and MATRICS Consensus Cognitive Battery (MCCB) was implemented to assess the cognitive impairment at baseline and day 20. Results showed that patients in the active rTMS group had more improvement in clinical symptoms and cognitive deficits than patients in sham group at day 20. In conclusion, 1 Hz rTMS over OFC can improve psychotic symptoms and cognitive functions in schizophrenic patients. Our study provides a new alternative for the treatment of negative symptoms and cognitive deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Left ventrolateral prefrontal cortex (VLPFC) has been demonstrated to be a crucial region involved in the down-regulation of negative affect by cognitive reappraisal. However, the neural evidence of causality is still lacking. The current study was to investigate the contribution of left VLPFC in cognitive reappraisal by using single-pulse transcranial magnetic stimulation (spTMS) and electroencephalogram (EEG). Fifteen participants repeated the cognitive reappraisal task at different TMS settings: no stimulation, spTMS applied at 300 ms after image onset to the left VLPFC, and to the vertex as a control site. EEG and behavioral data were concurrently recorded. TMS-evoked potential (TEP) and late positive potential (LPP) were investigated. In cognitive reappraisal, left VLPFC stimulation elicited stronger TEPs than vertex stimulation at 180 ms after TMS onset. Increased source activation of TEPs was identified in the precentral gyrus. Emotion regulation by reappraisal enlarged the trough of TEP at stimulation site. The left VLPFC stimulation led to enhanced LPP in cognitive reappraisal, which was negatively correlated with self-reported arousal. The TMS stimulation over left VLPFC influences the cognitive reappraisal process by potentiating the neural responses. Accordingly, the cortical region responsible for the execution of cognitive reappraisal is activated. The modulated neural activity is related to the behavioral response. The present study provided neural signatures for the facilitated execution of emotion regulation by left VLPFC stimulation, potentially contributing to the therapeutic protocols for mood disorders. • The intervention effects on cognitive reappraisal were investigated by TMS-EEG. • Excitatory effect was discovered by TMS evoked potential in left VLPFC stimulation. • Increased activation was found in the cortex responsible for regulation execution. • The late positive potential was negatively correlated with self-reported arousal. [ABSTRACT FROM AUTHOR]

Background Deficits in gamma-aminobutyric acid (GABA) inhibitory neurotransmission have been associated with pathophysiological mechanisms underlying schizophrenia. However, little is known about whether these deficits occur before or after the onset of psychosis. Method We recruited 16 drug-naive subjects at ultra-high risk of psychosis (UHR), 17 schizophrenia patients and 28 healthy controls. Cortical inhibition was determined using transcranial magnetic stimulation (TMS) over the left primary motor cortex. TMS markers such as short-interval cortical inhibition (SICI), cortical silent period (CSP) and intracortical facilitation (ICF) were obtained from each subject. While SICI can reflect GABA type A (GABA A ) mediated inhibition, CSP is thought to indicate GABA type B (GABA B ) mediated inhibitory circuits. Results As compared with healthy controls, UHR subjects showed a prolonged CSP with no change in SICI, whereas schizophrenia patients demonstrated both a prolonged CSP and a reduced SICI. No group differences were found for ICF. CSP in schizophrenia patients also had a positive correlation with positive symptom score of the positive and negative symptom scale (PANSS). Conclusions Cortical inhibitory deficits among UHR subjects were relatively limited compared to those among schizophrenia patients. Alterations might occur in some subgroup of GABA-mediated neurotransmitter systems before the onset of psychosis, while alterations in both GABA A and GABA B networks might contribute to full-blown psychosis. [ABSTRACT FROM AUTHOR]

Amphetamine-type stimulants are the second most commonly abused illicit drug worldwide, with no effective medical treatments currently available. Previous studies have demonstrated that high frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving in patients with methamphetamine dependence. However, the neuroplastic mechanism underlying rTMS intervention in methamphetamine users remains to be elucidated. Sixty participants (40 males) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either intermittent theta burst protocols (iTBS) (short bursts of 50 Hz rTMS repeated at a rate in the theta range (5 Hz), 2-sec on, 8-sec off for 5 min; 900 pulses) or sham rTMS over the DLPFC over four weeks (20 daily sessions). Resting state functional connectivity magnetic resonance imaging was acquired before and after rTMS intervention. Participants received drug related cue exposure and rated their craving before and after stimulation. Seed-based functional connectivity analysis was performed to probe rTMS-induced neuroplastic reorganization of brain functional networks. Results showed that twenty daily rTMS sessions decreased craving, increased functional connectivity between left DLPFC and inferior parietal lobule, and decreased functional connectivity between insula and inferior parietal lobule, medial temporal lobe and precuneus. Moreover, the increase of functional connectivity between DLPFC and inferior parietal lobule correlated with craving reduction. This study suggests that neuroplastic changes of frontoparietal functional connectivity contributes to craving reduction, shedding light on the therapeutic effect of rTMS on methamphetamine use disorder. This article is part of the special issue on Stress, Addiction and Plasticity. • rTMS reduce methamphetamine craving by neuroplastic mechanism. • Resting state functional connectivity reflects synchroplasticity in brain regions. • Changes of frontoparietal functional connectivity contribute to craving reduction. • Targeting DLPFC and insula provides potential solution to reduce craving. [ABSTRACT FROM AUTHOR]