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The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex-a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.

Self-agency is the awareness of being the agent of ones own thoughts and actions. Self-agency is essential for interacting with the outside world (reality-monitoring). The medial prefrontal cortex (mPFC) is thought to be one neural correlate of self-agency. We investigated whether mPFC activity can causally modulate self-agency on two different tasks of speech-monitoring and reality-monitoring. The experience of self-agency is thought to result from making reliable predictions about the expected outcomes of ones own actions. This self-prediction ability is necessary for the encoding and memory retrieval of ones own thoughts during reality-monitoring to enable accurate judgments of self-agency. This self-prediction ability is also necessary for speech-monitoring where speakers consistently compare auditory feedback (what we hear ourselves say) with what we expect to hear while speaking. In this study, 30 healthy participants are assigned to either 10 Hz repetitive transcranial magnetic stimulation (rTMS) to enhance mPFC excitability (N = 15) or 10 Hz rTMS targeting a distal temporoparietal site (N = 15). High-frequency rTMS to mPFC enhanced self-predictions during speech-monitoring that predicted improved self-agency judgments during reality-monitoring. This is the first study to provide robust evidence for mPFC underlying a causal role in self-agency, that results from the fundamental ability of improving self-predictions across two different tasks.

Parietal alpha activity shows a specific pattern of phasic changes during working memory. It decreases during the encoding and recall phases but increases during the maintenance phase. This study tested whether online rTMS delivered to the parietal cortex during the maintenance phase of a working memory task would increase alpha activity and hence improve working memory. Then, 46 healthy volunteers were randomly assigned to two groups to receive 3-day parietal 10 Hz online rTMS (either real or sham, 3600 pulses in total) that were time-locked to the maintenance phase of a spatial span task (180 trials in total). Behavioral performance on another spatial span task and EEG signals during a change detection task were recorded on the day before the first rTMS (pretest) and the day after the last rTMS (posttest). We found that rTMS improved performance on both online and offline spatial span tasks. For the offline change detection task, rTMS enhanced alpha activity within the maintenance phase and improved interference control of working memory at both behavioral (K score) and neural (contralateral delay activity) levels. These results suggested that rTMS with alpha frequency time-locked to the maintenance phase is a promising way to boost working memory.

Repetitive transcranial magnetic stimulation (rTMS) is a rapidly developing therapeutic modality for the safe and effective treatment of neuropsychiatric disorders. However, clinical rTMS driving systems and head coils are large, heavy, and expensive, so miniaturized, affordable rTMS devices may facilitate treatment access for patients at home, in underserved areas, in field and mobile hospitals, on ships and submarines, and in space. The central component of a portable rTMS system is a miniaturized, lightweight coil. Such a coil, when mated to lightweight driving circuits, must be able to induce B and E fields of sufficient intensity for medical use. This paper newly identifies and validates salient theoretical considerations specific to the dimensional scaling and miniaturization of coil geometries, particularly figure-8 coils, and delineates novel, key design criteria. In this context, the essential requirement of matching coil inductance with the characteristic resistance of the driver switches is highlighted. Computer simulations predicted E- and B-fields which were validated via benchtop experiments. Using a miniaturized coil with dimensions of 76 mm × 38 mm and weighing only 12.6 g, the peak E-field was 87 V/m at a distance of 1.5 cm. Practical considerations limited the maximum voltage and current to 350 V and 3.1 kA, respectively; nonetheless, this peak E-field value was well within the intensity range, 60-120 V/m, generally held to be therapeutically relevant. The presented parameters and results delineate coil and circuit guidelines for a future miniaturized, power-scalable rTMS system able to generate pulsed E-fields of sufficient amplitude for potential clinical use.

Non-invasive brain stimulation (NIBS) technologies, such as repetitive transcranial magnetic stimulation (rTMS), offer significant therapeutic potential for a growing number of neuropsychiatric conditions. Concurrent with the expansion of this field is the swift evolution of rTMS methodologies, including approaches to optimize stimulation site planning. Traditional targeting methods, foundational to early successes in the field and still widely employed today, include using scalp-based heuristics or integrating structural MRI co-registration to align the transcranial magnetic stimulation (TMS) coil with anatomical landmarks. Recent evidence, however, supports refining and personalizing stimulation sites based on the target's structural and/or functional connectivity profile. These connectomic approaches harness the network-wide neuromodulatory effects of rTMS to reach deeper brain structures while also enabling a greater degree of personalization by accounting for heterogenous network topology. In this study, we acquired baseline multimodal magnetic resonance (MRI) at two time points to evaluate the reliability and reproducibility of distinct connectome-based strategies for stimulation site planning. Specifically, we compared the intra-individual difference between the optimal stimulation sites generated at each time point for (1) functional connectivity (FC) guided targets derived from resting-state functional MRI and (2) structural connectivity (SC) guided targets derived from diffusion tensor imaging. Our findings suggest superior reproducibility of SC-guided targets. We emphasize the necessity for further research to validate these findings across diverse patient populations, thereby advancing the personalization of rTMS treatments. [ABSTRACT FROM AUTHOR]

Background: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. Methods: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance -- LTD) were measured. Results: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p<0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). Conclusions: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically assess the clinical efficacy of non-invasive brain stimulation (NIBS) for treating post-stroke sleep disorders (PSSD). Methods: We conducted thorough literature search across multiple databases, including PubMed, Web of Science, EmBase, Cochrane Library, Scopus, China Biology Medicine (CBM); China National Knowledge Infrastructure (CNKI); Technology Periodical Database (VIP), and Wanfang Database, focusing on RCTs examining NIBS for PSSD. Meta-analyses were performed using RevMan 5.4 and Stata 14. Results: Eighteen articles were reviewed, including 16 on repetitive Transcranial Magnetic Stimulation (rTMS), one on Theta Burst Stimulation (TBS), and two on transcranial Direct Current Stimulation (tDCS). Meta-analysis results indicated that rTMS within NIBS significantly improved the Pittsburgh Sleep Quality Index (PSQI) score (MD = −1.85, 95% CI [−2.99, −0.71], p < 0.05), the 17-item Hamilton Depression Rating Scale (HAMD-17) score [MD = −2.85, 95% CI (−3.40, −2.30), p < 0.05], and serum brain-derived neurotrophic factor (BDNF) levels [MD = 4.19, 95% CI (2.70, 5.69), p < 0.05], while reducing the incidence of adverse reactions [RR = 0.36, 95% CI (0.23, 0.55), p < 0.05]. TBS significantly improved the PSQI score in patients with PSSD (p < 0.05). Conversely, tDCS significantly improved the HAMD-17 score in PSSD patients [MD = −1.52, 95% CI (−3.41, −0.64), p < 0.05]. Additionally, rTMS improved sleep parameters, including Stage 2 sleep (S2%) and combined Stage 3 and 4 sleep (S3 + S4%) (p < 0.05), while tDCS improved total sleep time (TST) and sleep efficiency (SE) (p < 0.05).Subgroup analysis results indicated: (1) Both LF-rTMS and HF-rTMS improved PSQI scores (p < 0.05). (2) Both rTMS combined with medication and rTMS alone improved PSQI scores (p < 0.05). Compared to the sham/blank group, the rTMS group showed improvements in SE, sleep latency (SL), S1%, S3 + S4%, and REM sleep (REM%). The rTMS combined with medication group showed improved SL compared to the medication-only group (p < 0.05). Conclusion: NIBS effectively improves sleep quality, structure, depression levels, and BDNF levels in PSSD patients, while also being safe. Further investigations into the potential of NIBS in PSSD treatment may provide valuable insights for clinical applications. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42023485317. [ABSTRACT FROM AUTHOR]

Introduction: Broca's aphasia is a crushing syndrome after stroke. Although there are multiple therapies, the recovery of a considerable number of patients is still not ideal. Repetitive transcranial magnetic stimulation (rTMS) combined with speech and language therapy has been a promising combination regimen in recent years. However, the efficacy and persistent effects thereof remain unclear. We aimed to determine the immediate and long-term effects of rTMS combined with speech and language therapy on subacute stroke patients with Broca's aphasia and explore relevant mechanisms in the picture-naming task via functional near-infrared spectroscopy (fNIRS). Materials and methods: This was a prospective clinical study. In accordance with the inclusion criteria, 18 patients with post-stroke were recruited and randomly divided into either the rTMS group or the sham-rTMS group. Patients in both groups received low-frequency rTMS therapy for 20 min a day and then speech and language therapy for 30 min a day, 5 days a week, for a total of 4 weeks. Two groups of patients underwent the Western Aphasia Battery Revised (WAB-R), the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39), and non-language-based cognitive assessment (NLCA) before treatment and at 2 weeks, 4 weeks, and 3 months after treatment. Meanwhile, we collected fNIRS task state data while naming images before and after 4 weeks of treatment. The primary outcome was WAB-R changes. The secondary outcomes include the SAQOL-39, NLCA, as well as the difference in activation status of brain regions in the cortical language function network. Results: For the index scores of the two groups, the results of repeated-measures ANOVA indicated an increasing trend at three time points, i.e., after 2 weeks of treatment, 4 weeks after treatment, and 3 months after the end of treatment (p < 0.001); in terms of intergroup effects, there was a statistically significant difference between the two groups in WAB naming scores (F = 4.865, p = 0.042); and the aphasia quotient (AQ), listening comprehension, and naming scores of the two groups had interactive effects (F AQ = 11.316, P AQ = 0.000; F listening = 8.205, P listening = 0.002; F naming = 27.46, P naming = 0.000). Independent sample t-tests also showed that until 4 weeks after the end of treatment, there were significant differences in information volume and naming scores between the two groups (t information = 2.352, P information = 0.032; t naming = 3.164, P naming = 0.006). Three months after the end of treatment, there were significant differences in information volume, naming, AQ and repetition scores (t information = 2.824, P information = 0.012; t naming = 5.090, P naming = 0.000; t AQ = 2.924, P AQ = 0.010; t repetition = 2.721, P repetition = 0.015). In the picture-naming task, fNIRS analysis found that in the rTMS group after treatment, the activation in the left superior temporal gyrus (STG), middle temporal gyrus (MTG), premotor cortex (PM), supplementary motor area (SMA), pars triangularis Broca's area, and dorsolateral prefrontal lobe (DLPFC) decreased (p < 0.05). Conclusion: The language function of patients was improved after 4 weeks of treatment, and there was a long-term effect (3 months follow-up), especially in naming gains. Moreover, by analyzing cortical activation during a picture-naming task with fNIRS, we found that rTMS could downgrade the activation level in the left MTG, STG, PM and SMA, DLPFC, and pars triangularis Broca's area, whereas the sham-rTMs group only showed downgraded activation levels in the right PM and SMA. This demonstrates the unique mechanism of rTMS. Clinical trial registration : ChiCTR.org.cn, identifier, ChiCTR2300067703. [ABSTRACT FROM AUTHOR]

Background: Intermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation technique, is recognized for its ability to modulate cortical neuronal activity. However, its effects over time and the dynamics following stimulation are less well understood. Understanding the temporal dynamics of iTBS effects is essential for optimizing the timing and frequency of stimulation in therapeutic applications. Objective: This study investigated the temporal changes in protein expression induced by iTBS in Neuro-2a cells. Methods: We analyzed protein expression in retinoic acid-differentiated Neuro-2a cells at multiple time points — 0.5, 3, 6, 12, and 24 hours post-iTBS — using Western blot and immunocytochemistry techniques. Results: Our findings reveal a significant early increase in neurotransmitter receptor subunits, neurotrophic factors, and cytoskeletal proteins within the first 0.5 hour following iTBS. Notably, proteins such as mGLuR1, NMDAR1, GABBR2, and β-tubulin III showed substantial increase in expression. However, the effects of iTBS on protein expression was not sustained at later timepoints. Conclusion: Our results suggest that iTBS can transiently alter the expression of specific proteins in Neuro-2a cells. Future research should investigate the potential benefits of repeated stimulations within the early time window to refine iTBS interventions, potentially expanding their research and clinical applications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This study aimed to elucidate the effects of repetitive transcranial magnetic stimulation (rTMS) on weight, body mass index (BMI), and lipid metabolism in patients with treatment‐resistant depression (TRD).This retrospective observational study included patients with TRD who received rTMS treatment at the Jikei University Hospital from September 2018 to August 2021. The patients were diagnosed based on the DSM‐5 and ICD‐10 criteria and treated using the NeuroStar TMS System. For 3–6 weeks, 10‐Hz rTMS was administered to the left dorsolateral prefrontal cortex at 120% motor threshold. The primary outcomes were changes in weight and BMI, whereas the secondary outcomes included changes in total, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL) cholesterol levels, thyroid function indicators, as well as HAMD‐17, HAMD‐24, and Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Statistical analysis was conducted using paired t‐tests and repeated measures ANOVA.Among the 34 patients (20 men and 14 women) included, no significant changes were observed in weight or BMI after rTMS treatment (average weight reduction: −0.50 kg, 95% CI: −0.14 to 0.56, p = 0.24; average BMI reduction: −0.21, 95% CI: −0.10 to 0.61, p = 0.15). However, significant reductions in total, HDL, and LDL cholesterol levels and FT4 were observed. Furthermore, the HAMD‐17, HAMD‐24, and MADRS scores significantly increased post‐treatment.rTMS treatment did not affect weight or BMI in patients with TRD but is believed to improve lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Epilepsy is one of the most prevalent brain diseases. Approximately one third of patients consistently experience drug‐resistant epilepsy (DRE), a condition where seizures persist despite the use of antiseizure medications. Exploration of new therapies for DRE is urgently needed. In this single‐center, randomized, sham‐controlled, crossover clinical trial (NCT05042726), we aimed to investigate the effectiveness and safety of transcranial magnetic continuous theta burst stimulation (cTBS) targeting the cerebellum to treat DRE.Patients with DRE for ≥2 years and a seizure frequency of ≥2 seizures per month were enrolled and randomized 1:1 to receive active stimulation followed by sham stimulation or vice versa. The bilateral cerebellum was targeted by navigated cTBS focusing on the cerebellar dentate nucleus, once daily on workdays for 2 weeks. The primary outcomes were the percentage of seizure reduction and 50% responder rate in the per‐protocol population within 2 months after treatment.Forty‐four patients were enrolled and randomized; 18 patients in the active stimulation‐first group and 20 in the sham stimulation‐first group were included in the final analysis. Active cTBS significantly reduced seizures compared to sham stimulation (difference in percentage of seizure reduction between treatments = 25%, 95% confidence interval [CI] = 5%–46%, p = .018). The 50% responder rate after active stimulation was significantly higher than that after sham stimulation (difference in 50% responder rate between treatments = 24%, 95% CI = 11%–40%, p = .029). Adverse events occasionally occurred during active stimulation (moderate headache in 5% of patients, tinnitus in 3% of patients, dizziness in 3% of patients) but resolved spontaneously within days after treatment completion.This trial suggested that cTBS targeting the cerebellum was effective and well tolerated in the treatment of DRE. Further studies are warranted to confirm its effectiveness and mechanism. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Selective serotonin reuptake inhibitors are thought to exert a clinical effect through various mechanisms, including through alteration in synaptic plasticity. Repetitive transcranial magnetic stimulation can induce temporary changes in synaptic excitability in cerebral cortex that resemble long‐term potentiation and long‐term depression that serve as a measure of synaptic plasticity in vivo. A version of repetitive transcranial magnetic stimulation called continuous theta burst stimulation can induce inhibition of cortical excitability that can be measured through a motor evoked potential. Previous work has suggested that this response can be modulated by administration of selective serotonin reuptake inhibitors.Thirty‐one healthy volunteers received both fluoxetine 20 mg and placebo in randomly ordered sessions, followed by spaced continuous theta burst stimulation to motor cortex. Changes in Motor Evoked Potentials were then recorded over 60 min.The response to spaced continuous theta burst stimulation did not differ significantly between fluoxetine and placebo sessions. Spaced continuous theta burst stimulation produced a paradoxical excitatory response in an unexpected number of participants.A single dose of fluoxetine 20 mg does not influence the response to continuous theta burst stimulation. Previous results suggesting an effect of selective serotonin reuptake inhibitors on inhibitory non‐invasive brain stimulation protocols may be due to insufficiently large sample sizes. [ABSTRACT FROM AUTHOR]

Introduction: Voxel-based morphometry (VBM) was applied to explore structural changes induced by repetitive transcranial magnetic stimulation (rTMS) and the relationship with clinical outcomes. Moreover, the relationship between each segmented regional gray matter (GM) volume was investigated to identify circuits involved in the rTMS treatment process in patients with drug-resistant epilepsy (DRE). Methods: Nineteen patients with DRE were finally included in the analysis. A session of rTMS was applied for 5 consecutive days. Participants received either 1,000 or 3,000 pulses, at a frequency of 0.5 Hz and the intensity was set at 90% of the individual's resting motor threshold. VBM analysis was performed to explore regional GM volume changes 2 months after rTMS application. The regional volume change was correlated with seizure reduction rate. Relationships between changes in GM volume in each anatomically parcellated region were analyzed using a fully-automated segmentation pipeline. Results: Compared to the baseline, seizure frequency was reduced, and quality of life was improved after rTMS treatment. Regional volume was increased in the cerebellar vermis 2 months after rTMS application. The increased cerebellar vermis volume correlated with the reduced seizure frequency. Regional volume changes in the cerebellar vermis were correlated with changes in the subcortical and cortical GM regions including the thalamus, caudate, and frontal cortex. Discussion: These results indicate that rTMS treatment effectively reduced seizure frequency in patients with DRE. Increased volume in the cerebellar vermis and activations of the cerebello-thalamo-cortical circuit may be a crucial mechanism underlying the effectiveness of rTMS application in patients with DRE. [ABSTRACT FROM AUTHOR]

The editorial titled "How does brain stimulation work? Neuroversion and other putative mechanisms of action" explores the evolving field of brain stimulation techniques in psychiatry and neurology. It discusses various methods such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS) that trigger neurochemical and electrophysiological changes in the brain to produce therapeutic effects. The research topic includes 10 articles authored by 76 individuals covering a range of brain stimulation techniques and their applications in neuropsychiatric disorders, aiming to enhance understanding and influence further research and clinical practice. The findings presented in the editorial highlight the diverse applications of brain stimulation techniques and their potential benefits, contributing to the advancement of clinical practice and stimulating further investigation into the mechanisms underlying these therapies. [Extracted from the article]

Introduction: While repetitive transcranial magnetic stimulation (rTMS) is effective for 50-60% of those treatment-resistant depression, it is critical to identify predictors of response for optimal patient selection to improve therapy. Insomnia is a known symptom of depression that is both correlated with depression severity and associated with poor antidepressant response. Therefore, understanding this relationship may open new opportunities for the optimization of rTMS treatment. We aimed to explore whether baseline sleep quality, specifically insomnia, is associated with rTMS outcomes in a naturalistic sample of 975 patients (age 18-90; 63.9% F) receiving a standard course of rTMS treatment from two outpatient TMS clinics located within psychiatric hospitals in the United States. One site additionally collected information on concurrent medication use on 350 patients; among these, we examined whether pharmacological treatment of insomnia affected TMS treatment response. Methods: Depression was measured using the 30-item Inventory of Depressive Symptomology Self Report (IDS-SR) in site one and an abbreviated 16-item Quick Inventory of Depressive Symptomology (QIDS) derived from the IDS-SR in site two. Sleep disturbances were measured using three insomnia-related questions. Multilevel logistic regression was used to determine whether baseline insomnia scores were associated with TMS treatment outcome. Upon dichotomous categorization of the sample by insomnia and sleep-medication use, depression and sleep scores were analyzed across time using mixed repeated measures ANOVA. Results: We found that sleep quality improves after TMS (p<.001) and correlates with improvement in non-insomnia related depression symptoms (r=.318, p<.001). We found that among those who had significant insomnia at baseline, those not using sleep medications had significantly worse post-treatment IDS-SR scores compared to those using sleep medications (p=. 021) despite no difference in final insomnia score. Discussion: Together, our results suggest that while baseline insomnia is not associated with TMS effectiveness, treating insomnia may affect the trajectory of TMS therapy. Future prospective studies are needed to examine the effect of insomnia treatment alongside TMS for depression. [ABSTRACT FROM AUTHOR]

Drug-resistant mental disorders, particularly treatment-resistant depression, pose a significant medical and social problem. To address this challenge, modern psychiatry is constantly exploring the use of novel treatment methods, including biological treatments, such as transcranial magnetic stimulation (TMS), and novel rapid-acting antidepressants, such as ketamine. While both TMS and ketamine demonstrate high effectiveness in reducing the severity of depressive symptoms, some patients still do not achieve the desired improvement. Recent literature suggests that combining these two methods may yield even stronger and longer-lasting results. This review aims to consolidate knowledge in this area and elucidate the potential mechanisms of action underlying the increased efficacy of combined treatment, which would provide a foundation for the development and optimization of future treatment protocols. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) remains a significant global health concern. The progression from preclinical stages to overt dementia has become a crucial point of interest for researchers. This paper reviews the potential of neurophysiological biomarkers in predicting AD progression, based on a systematic literature search following PRISMA guidelines, including 55 studies. EEG-based techniques have been predominantly employed, whereas TMS studies are less common. Among the investigated neurophysiological measures, spectral power measurements and event-related potentials-based measures, including P300 and N200 latencies, have emerged as the most consistent and reliable biomarkers for predicting the likelihood of conversion to AD. In addition, TMS-based indices of cortical excitability and synaptic plasticity have also shown potential in assessing the risk of conversion to AD. However, concerns persist regarding the methodological discrepancies among studies, the accuracy of these neurophysiological measures in comparison to established AD biomarkers, and their immediate clinical applicability. Further research is needed to validate the predictive capabilities of EEG and TMS measures. Advancements in this area could lead to cost-effective, reliable biomarkers, enhancing diagnostic processes and deepening our understanding of AD pathophysiology. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Methods: Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. Results: The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA – ipsilateral cerebellum) changes and BBS changes in SMA group. Discussion: In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. Clinical trial registration: Registration number: ChiCTR2200060955, https://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta‐analysis aimed to assess the effectiveness of non‐invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). Objective: We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. Methods: The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta‐analysis was performed. Results: Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = −2.49, [95% confidence interval: −3.34, −1.64]) and ICARS (−5.27 [−7.06, −3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. Conclusion: Non‐invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high‐quality RCTs are required. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the cerebellum contributes to contraction-induced facilitation (CIF) of contralateral corticospinal excitability. To this end, repetitive cerebellar transcranial magnetic stimulation (TMS) was used to test whether it modulates CIF. Overall, 20 healthy young individuals participated in the study. Single-pulse TMS was applied to the left primary motor cortex to induce motor-evoked potentials (MEP) on electromyography of the right first dorsal interosseous (FDI) muscle to test corticospinal excitability. This measurement was conducted during contraction (10% maximum voluntary contraction [MVC]) and rest (0% MVC) of the FDI muscle. CIF, cerebellar brain inhibition (CBI), cortical silent period (cSP), and resting motor threshold (rMT) were measured before and after low-frequency repetitive TMS (crTMS) of the right cerebellum to downregulate cerebellar output. The CIF (contraction/rest of the MEP), CBI (conditioned/unconditioned MEP) during contraction, cSP, and rMT were not affected by crTMS. At rest, CBI was decreased. These findings indicated that the primary motor cortex function for the increase in corticospinal excitability was not affected by crTMS. This study contributes to our understanding of the role of the cerebellum in motor control. Additionally, it may inform decision-making for the site of cerebellar ataxia treatment using non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

The experience of pain that is induced by extremely cold temperatures can exert a modulatory effect on motor cortex circuitry. Although it is known that immersion of a single limb in very cold water can increase corticomotor excitability it is unknown how afferent input to the cortex shapes excitatory and inhibitory processes. Therefore, the purpose of this study was to examine motor‐evoked potentials (MEP), short‐latency afferent inhibition (SAI) and long‐latency afferent inhibition (LAI) in response to immersion of a single hand in cold water. Transcranial magnetic stimulation (TMS) was used to assess MEPs, and peripheral nerve stimulation of the median nerve paired with TMS was used to measure SAI and LAI in motor circuits of the ipsilateral hemisphere. Measurements were obtained from electromyography (EMG) of the first dorsal interosseous (FDI) at baseline, during cold‐water immersion, and during recovery from cold‐water immersion. The intervention caused unconditioned MEPs to increase during exposure to the cold stimulus (P = 0.008) which then returned to baseline levels once the hand was removed from the cold water. MEP responses were decoupled from SAI responses, where SAI was reduced during exposure to the cold stimulus (P = 0.005) and remained reduced compared to baseline when the hand was removed from the cold water (P = 0.002). The intervention had no effect on LAI. The uncoupling of SAI from MEPs during the recovery period suggests that the mechanisms underlying the modulation of corticospinal excitability by sensory input may be distinct from those affecting intracortical inhibitory circuits. Highlights: What is the central question of this study?Does immersion of a limb in very cold water influence corticospinal excitability and the level of afferent inhibition exerted on motor cortical circuits?What is the main finding and its importance?In additional to perception of temperature, immersion in 6°C water also induced perceptions of pain. Motor evoked potential (MEP) amplitude increased during immersion, and short‐latency afferent inhibition (SAI) of the motor cortex was reduced during immersion; however, these responses differed after the limb was removed from the cold stimulus, as MEPs returned to normal levels while SAI remained suppressed. [ABSTRACT FROM AUTHOR]

With over 16 years of experience in clinical, research, and educational activities related to transcranial magnetic stimulation (TMS), I have written this article exploring the ethical dimensions of TMS. This article aims to provide valuable and informative content for those unfamiliar with TMS as well as those just starting in the field. Specifically, this article elaborates on four principles of medical ethics, including those applicable to TMS therapy, the disparity between public medical insurance coverage and medical indications in private practice for TMS therapy, and issues concerning research ethics in practice. I also provide recommendations regarding roles and strategies for adoption by academia and those in this field dedicated to making TMS therapy accessible to a larger patient population in a suitable manner. Lastly, it is my hope that this article will serve as a contemporary "Ethics of TMS Neuromodulation", resonating with the inherent human pursuit of "truth, goodness, and beauty" for a sound mind and spirit. [ABSTRACT FROM AUTHOR]

Dual-mode non-invasive brain stimulation using repetitive transcranial magnetic stimulation and transcranial direct current stimulation is known to help neurorehabilitation in patients with stroke. However, this neuromodulation effect may vary depending on the lesion location of patients with stroke, and the basis in lesion location for this is insufficient. This study aims to investigate the difference in neuromodulation effectiveness according to the lesion location after dual-mode brain stimulation using electroencephalography signals. Eight patients with ischemic subacute stroke and 11 healthy controls participated in this study. Brain stimulation was conducted in one session per day for a total of 10 days over the motor cortex, electroencephalography was measured for 5 min with eyes closed, and motor function was evaluated before and after dual-mode stimulation. The lesion location was divided into an infratentorial stroke (ITS) and a supratentorial stroke (STS) based on tentorium cerebelli. In addition, we focused on the mu and beta bands related to motor function. In terms of intrahemispheric connectivity, the mu weighted phase lag index over the contralesional primary motor cortex was significantly higher in only ITS before stimulation compared to healthy controls, and mu Granger causality over the ipsilesional primary motor cortex was significantly higher in both ITS and STS after stimulation compared to healthy controls. In contrast, from the perspective of interhemispheric connectivity, the laterality of beta Granger causality before stimulation in ITS was lower than that of healthy controls and significantly increased after stimulation. The effect of brain stimulation may vary depending on the lesion location of patients with stroke, and these findings provide indicative insights into effective dual-mode stimulation interventions for neurorehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear. Methods: To further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based eventrelated potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory thetaburst stimulation--a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)--over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices. Results: The results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials ("Gratton effect") that was only accomplished with an intact DLPFC (i.e., following placebo stimulation). Discussion: Because non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities. [ABSTRACT FROM AUTHOR]

Background: Postural instability and gait disorder and cognitive dysfunction are common symptoms of Parkinson’s disease (PD). Scale assessment is frequently used in the clinic to evaluate PD, but this technique is limited by its lack of sensitivity to changes in disease progression and its difficulty in capturing subtle movements and changes in cognitive function. It is currently believed that high-frequency repetitive transcranial magnetic stimulation (rTMS) can improve motor and cognitive dysfunction in patients with PD, though it remains controversial. Therefore, it is imperative to monitor and dynamically identify changes in postural instability and gait disorder, as well as those in cognitive dysfunction, in PD to develop targeted interventions. In this study, we observed the effect of high-frequency rTMS on gait disorders and cognitive functions in patients with PD by comparing data from wearable devices and eye-tracking devices before and after treatment. Methods: A total of 159 patients with PD were included in this study. A GYENNO MATRIX wearable gait analyzer was used to monitor the objective gait data (including the timed up-and-go, narrow-track, and turning tests), the Eyeknow eye-tracking evaluation system was used to monitor the patient’s eye movement cognition data (including the smooth pursuit, pro-saccade, and anti-saccade tests), and gait and cognitive function–related scales, including the Tinetti Balance Scale, Tinetti Gait Scale, Berg Balance Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment (MoCA), were evaluated at the same time before and after high-frequency rTMS treatment. Results: The mean step length, mean stride velocity, stride length, and mean step frequency of patients with PD in the timed up-and-go test all increased compared with those before rTMS treatment, whereas the mean stride time and double support decreased. In the narrow-track test, the mean stride velocity increased and the mean stride time decreased. In the turning test, the turning left duration, turning right duration, mean duration, mean number of steps, and average step duration decreased, while the mean angular velocity increased after rTMS treatment. Compared with those before rTMS treatment, the latency period of patients with PD in overlapping saccades decreased, the completion time of overlapping saccades decreased, and the average saccade speed increased. In the anti-saccade test, the completion time decreased and the average saccade speed increased after rTMS treatment. Compared with those before rTMS treatment, the Tinetti Balance Scale, Tinetti Gait Scale, Berg Balance Scale, Mini-Mental State Examination, and MoCA scores increased, and the MoCA sub-items improved in terms of visual–spatial and executive function, language, abstraction, delayed recall, and orientation after rTMS treatment. Conclusion: High-frequency rTMS may be an effective therapy for improving gait disorders and cognitive functions in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. Methods: This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10- Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results: Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. Conclusion: This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on motor function and cortical excitability in stroke patients with different motor evoked potential (MEP) status. Methods: A total of 80 stroke patients were enrolled in this randomized controlled trial and divided into two groups according to MEP status (- or +) of lesioned hemisphere. Then, each group was randomly assigned to receive either active or sham LF-rTMS. In addition to conventional rehabilitation, all participants received 20 sessions of rTMS at 1 Hz frequency through the active or the sham coil over 4 weeks. Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale (NIHSS), Shoulder Abduction Finger Extension (SAFE) and Barthel Index (BI), bilateral resting motor threshold (rMT), amplitude of Motor evoked potential (MEP) and Central Motor Conduction Time (CMCT), and Interhemispheric asymmetry (IHA) were blindly assessed at baseline, 4 weeks and 8 weeks after treatment, respectively. Results: At 4 weeks after intervention, FMA and NIHSS changed scores in 1 Hz MEP(+) group were significantly higher than those in the other three groups (p < 0.001). After receiving 1 Hz rTMS, stroke patients with MEP(+) showed significant changes in their bilateral cortical excitability (p < 0.05). At 8 weeks after intervention, 1 Hz MEP(+) group experienced higher changes in NIHSS, FMA, SAFE, and BI scores than other groups (p < 0.001). Furthermore, 1 Hz rTMS intervention could decrease unaffected cortical excitability and enhance affected cortical excitability of stroke patients with MEP(+) (p < 0.05). The correlation analysis revealed that FMA motor change score was associated with decreased unaffected MEP amplitude (r = -0.401, p = 0.010) and decreased affected rMT (r = -0.584, p < 0.001) from baseline, which was only observed in the MEP(+) group. Conclusion: The effects of LF-rTMS on motor recovery and cortical excitability were more effective in stroke patients with MEP than those with no MEP. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may be an effective and safe alternative treatment for post-stroke cognitive impairment (PSCI). Similarly, the application of transcranial direct current stimulation (tDCS) during stroke rehabilitation has been shown to improve cognitive function in PSCI patients. However, there have been conflicting results from some studies. Therefore, this study aims to conduct a meta-analysis to evaluate the effects of tDCS and rTMS on PSCI. Methods: The meta-analysis search for articles published from the initial availability date to 5 February 2024 in databases. The extracted study data were entered into STATA 12.0 software for statistical analysis. Results: This meta-analysis provides evidence that both rTMS and tDCS have a positive impact on general cognitive function in PSCI patients [immediate effect of rTMS: standard mean difference (SMD) = 2.58, 95% confidence interval (CI) = 1.44 to 3.71; long-term effect of rTMS: SMD = 2.33, 95% CI = 0.87-3.78; immediate effect of tDCS: SMD = 2.22, 95% CI = 1.31-3.12]. Specifically, rTMS was found to significantly improve attention, language, memory, and visuospatial functions, while it did not show a significant therapeutic effect on executive function (attention: SMD = 3.77, 95% CI = 2.30-5.24; executive function: SMD = -0.52, 95% CI = -3.17-2.12; language: SMD = 3.43, 95% CI = 1.50-5.36; memory: SMD = 3.52, 95% CI = 1.74-5.30; visuospatial function: SMD = 4.71, 95% CI = 2.61-6.80). On the other hand, tDCS was found to significantly improve executive and visuospatial functions but did not show a significant improvement in attention function and memory (attention: SMD = 0.63, 95% CI = -0.30-1.55; executive function: SMD = 2.15, 95% CI = 0.87-3.43; memory: SMD = 0.99, 95% CI = -0.81-2.80; visuospatial function: SMD = 2.64, 95% CI = 1.04-4.23). Conclusion: In conclusion, this meta-analysis demonstrates that both rTMS and tDCS are effective therapeutic techniques for improving cognitive function in PSCI. However, more large-scale studies are needed to further investigate the effects of these techniques on different cognitive domains in PSCI. [ABSTRACT FROM AUTHOR]

Meta-learning enables us to learn how to learn the same or similar tasks more efficiently. Decision-making literature theorizes that a prefrontal network, including the orbitofrontal and anterior cingulate cortices, underlies meta-learning of decision making by reinforcement learning. Recently, computationally similar meta-learning has been theorized and empirically demonstrated in motor adaptation. However, it remains unclear whether meta-learning of motor adaptation also relies on a prefrontal network. Considering hierarchical information flow from the prefrontal to motor cortices, this study explores whether meta-learning is processed in the dorsolateral prefrontal cortex (DLPFC) or in the dorsal premotor cortex (PMd), which is situated upstream of the primary motor cortex, but downstream of the DLPFC. Transcranial magnetic stimulation (TMS) was delivered to either PMd or DLPFC during a motor meta-learning task, in which human participants were trained to regulate the rate and retention of motor adaptation to maximize rewards. While motor adaptation itself was intact, TMS to PMd, but not DLPFC, attenuated meta-learning, impairing the ability to regulate motor adaptation to maximize rewards. Further analyses revealed that TMS to PMd attenuated meta-learning of memory retention. These results suggest that meta-learning of motor adaptation relies more on the premotor area than on a prefrontal network. Thus, while PMd is traditionally viewed as crucial for planning motor actions, this study suggests that PMd is also crucial for meta-learning of motor adaptation, processing goal-directed planning of how long motor memory should be retained to fit the long-term goal of motor adaptation. [ABSTRACT FROM AUTHOR]

Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel technique for noninvasive brain stimulation (NIBS). TUS delivered in a theta (5 Hz) burst pattern (tbTUS) induces plasticity in the human primary motor cortex (M1) for 30–60 min, showing promise for therapeutic development. Metaplasticity refers to activity-dependent changes in neural functions governing synaptic plasticity; depotentiation is the reversal of long-term potentiation (LTP) by a subsequent protocol with no effect alone. Metaplasticity can enhance plasticity induction and clinical efficacy of NIBS protocols. In our study, we compared four NIBS protocol combinations to investigate metaplasticity on tbTUS in humans of either sex. We delivered four interventions: (1) sham continuous theta burst stimulation with 150 pulses (cTBS150) followed by real tbTUS (tbTUS only), (2) real cTBS150 followed by sham tbTUS (cTBS only), (3) real cTBS150 followed by real tbTUS (metaplasticity), and (4) real tbTUS followed by real cTBS150 (depotentiation). We measured motor-evoked potential amplitude, short-interval intracortical inhibition, long-interval intracortical inhibition, intracortical facilitation (ICF), and short-interval intracortical facilitation before and up to 90 min after plasticity intervention. Plasticity effects lasted at least 60 min longer when tbTUS was primed with cTBS150 compared with tbTUS alone. Plasticity was abolished when cTBS150 was delivered after tbTUS. cTBS150 alone had no significant effect. No changes in M1 intracortical circuits were observed. Plasticity induction by tbTUS can be modified in manners consistent with homeostatic metaplasticity and depotentiation. This substantiates evidence that tbTUS induces LTP-like processes and suggests that metaplasticity can be harnessed in the therapeutic development of TUS. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat various neurological disorders. However, the molecular mechanism underlying the therapeutic effect of rTMS on Parkinson's disease (PD) has not been fully elucidated. Neuroinflammation like regulatory T-cells (Tregs) appears to be a key modulator of disease progression in PD. If rTMS affects the peripheral Tregs in PD remains unknown. Methods: Here, we conducted a prospective clinical study (Chinese ClinicalTrials. gov: ChiCTR 2100051140) involving 54 PD patients who received 10-day rTMS (10 Hz) stimulation on the primary motor cortex (M1) region or sham treatment. Clinical and function assessment as well as flow cytology study were undertaken in 54 PD patients who were consecutively recruited from the department of neurology at Zhujiang hospital between September 2021 and January 2022. Subsequently, we implemented flow cytometry analysis to examine the Tregs population in spleen of MPTP-induced PD mice that received rTMS or sham treatment, along with quantitative proteomic approach reveal novel molecular targets for Parkinson's disease, and finally, the RNA interference method verifies the role of these new molecular targets in the treatment of PD. Results: We demonstrated that a 10-day rTMS treatment on the M1 motor cortex significantly improved motor dysfunction in PD patients. The beneficial effects persisted for up to 40 days, and were associated with an increase in peripheral Tregs. There was a positive correlation between Tregs and motor improvements in PD cases. Similarly, a 10-day rTMS treatment on the brains of MPTP-induced PD mice significantly ameliorated motor symptoms. rTMS reversed the downregulation of circulating Tregs and tyrosine hydroxylase neurons in these mice. It also increased anti-inflammatory mediators, deactivated microglia, and decreased inflammatory cytokines. These effects were blocked by administration of a Treg inhibitor anti-CD25 antibody in MPTP-induced PD mice. Quantitative proteomic analysis identified TLR4, TH, Slc6a3 and especially Syt6 as the hub node proteins related to Tregs and rTMS therapy. Lastly, we validated the role of Treg and rTMS-related protein syt6 in MPTP mice using the virus interference method. Conclusions: Our clinical and experimental studies suggest that rTMS improves motor function by modulating the function of Tregs and suppressing toxic neuroinflammation. Hub node proteins (especially Syt6) may be potential therapeutic targets. Trial registration: Chinese ClinicalTrials, ChiCTR2100051140. Registered 15 December 2021, https://www.chictr.org.cn/bin/project/edit?pid=133691 rTMS is a safe and non-invasive method for Parkinson's disease. In this study, we showed the proportion of CD4+CD25+CD127- regulatory T-cells (Tregs) in the peripheral blood was significantly increased after rTMS treatment. Similar effects of rTMS treatment were verified in MPTP-induced PD mice. Proteomic analysis and RNA interference analyses identified TLR4, TH, Slc6a3 and especially Syt6 as hub node proteins that can be modulated by rTMS therapy in PD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that shows promise as a potential treatment for depression. However, the clinical efficacy of tDCS varies, possibly due to individual differences in head anatomy affecting tDCS dosage. While functional changes in brain activity are more commonly reported in major depressive disorder (MDD), some studies suggest that subtle macroscopic structural differences, such as cortical thickness or brain volume reductions, may occur in MDD and could influence tDCS electric field (E-field) distributions. Therefore, accounting for individual anatomical differences may provide a pathway to optimize functional gains in MDD by formulating personalized tDCS dosage. Methods: To address the dosing variability of tDCS, we examined a subsample of sixteen active-tDCS participants' data from the larger ELECT clinical trial (NCT01894815). With this dataset, individualized neuroimaging-derived computational models of tDCS current were generated for (1) classifying treatment response, (2) elucidating essential stimulation features associated with treatment response, and (3) computing a personalized dose of tDCS to maximize the likelihood of treatment response in MDD. Results: In the ELECT trial, tDCS was superior to placebo (3.2 points [95% CI, 0.7 to 5.5; P = 0.01]). Our algorithm achieved over 90% overall accuracy in classifying treatment responders from the active-tDCS group (AUC = 0.90, F1 = 0.92, MCC = 0.79). Computed precision doses also achieved an average response likelihood of 99.981% and decreased dosing variability by 91.9%. Conclusion: These findings support our previously developed precision-dosing method for a new application in psychiatry by optimizing the statistical likelihood of tDCS treatment response in MDD. [ABSTRACT FROM AUTHOR]

Background: This study aimed to observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function and thyroid hormone levels in early older stroke patients with low thyroid hormone levels, and to investigate the correlation between the changes in thyroid hormone levels and the improvements in cognitive function after stroke. Methods: Forty older stroke patients who met the inclusion criteria were recruited and randomized into a magnetic-stimulation group (rTMS group) and a sham-stimulation group (Sham group). The rTMS group received lowfrequency true stimulation and the Sham group received low-frequency sham stimulation. Patients' cognitive scores, activity of daily living(ADL) scores, and their levels of triiodothyronine (T3), free triiodothyronine (FT3), thyroxin (T4), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were assessed before the intervention, after the 4-week intervention, and after an additional 4 weeks of follow-up; Repeated measurement analysis of variance was used to compare the changes of each index in the two groups at different times and the correlations between patiens' cognitive function scores and their changing hormone levels were subsequently investigated. Results: Thirty-one patients were included in this study: 16 patients in rTMS group and 15 patients in the Sham group. Repeated-measures ANOVA showed that patients' T3, FT3 and TSH levels tended to increase at 4-week intervention and at the follow up (p < 0.05), and that the rTMS group had a better effect on improving T3 than the Sham group (Fgroup = 5.319, p = 0.028); The cognitive scale at different time points in both groups showed an upward trend (p < 0.05), and the MoCA, DSF, DSB scores in the rTMS group were statistically higher than those in the Sham group at the end of the 4-week intervention and at the follow-up (p < 0.05); The changes in the levels of T3 before and after 4-week intervention were positively correlated with the changes in the MoCA scores (r = 0.638, p < 0.05). And the difference in T3 level change was positively correlated with the difference in delayed recall, attention and naming score change (r = 0.562, p < 0.05; r = 0.562, p < 0.05; r = 0.531, p < 0.05); and the difference in FT3 level change was positively correlated with the visuospatial and executive function (r = 0.514, p < 0.05). Conclusion: Repetitive transcranial magnetic stimulation improved cognitive function and elevated T3 levels in older patients with post-stroke cognitive dysfunction who had low thyroid hormone levels. Within the normal range, increases in T3 levels are positively correlated with changes in cognitive function. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal depression is a serious and highly prevalent medical condition in the USA. Nearly 85% of individuals with perinatal depression go untreated, leading to significant morbidity and mortality. There is an urgent need to develop and advance safe and effective treatments for perinatal depression. Transcranial magnetic stimulation is an established intervention for depression in non-pregnant individuals yet is not well studied in perinatal depression. Case presentation: A 33-year-old pregnant Latina female presented with severe, recurrent, treatment-resistant depression and suicidal ideation. The patient had previously trialed psychotherapy, multiple antidepressants, and mood stabilizers and had achieved remission with lithium prior to pregnancy. Due to pregnancy and fetal safety concerns, the patient discontinued lithium and consequently suffered progressive worsening of perinatal depression. At 24 weeks gestation and after additional failed medication trials, a prolonged course of transcranial magnetic stimulation was initiated. Following 46 transcranial magnetic stimulation treatments over 9 weeks using two protocol types (repetitive transcranial magnetic stimulation and intermittent theta burst stimulation), she achieved near-remission of perinatal depression and resolution of suicidal ideation. There were no identified maternal or fetal adverse events at 6 weeks post-delivery. Conclusion: To our knowledge, this is the first published case of a pregnant individual with perinatal depression who received and tolerated a prolonged transcranial magnetic stimulation course with two distinct protocols (repetitive transcranial magnetic stimulation and intermittent theta burst stimulation) with clinically significant response. Transcranial magnetic stimulation is a well-tolerated and effective intervention that warrants further investigation for use in treatment-resistant perinatal depression. Key Points: Perinatal depression is a serious and potentially life-threatening condition with long-term maternal and fetal adverse outcomes. While antidepressants and psychotherapy are considered first-line treatments for perinatal depression, there is limited efficacy in treatment-resistant perinatal depression. Transcranial magnetic stimulation has potential as an effective, well-tolerated, alternative modality for treatment- resistant perinatal depression that warrants further investigation. Future studies of transcranial magnetic stimulation in treatment-resistant perinatal depression should explore different protocols to determine the optimal approach for this population. [ABSTRACT FROM AUTHOR]

Background: Balance dysfunction affects 70% of stroke patients. Emerging neurophysiological approaches, such as virtual reality therapy (VRT) and repetitive transcranial magnetic stimulation (rTMS), have been proven by clinical studies that the balance function of stroke patients can be improved when applied alone, but there are relatively few studies on the combined treatment of balance dysfunction after stroke. This study aimed to evaluate the impact of a 4-week intensive intervention combining VRT and rTMS on both balance function and brain plasticity among stroke patients. Methods: This single-blind, randomized controlled trial was conducted at the Rehabilitation Medical Center of the Rehabilitation General Hospital of Ningxia Medical University. A cohort of 136 stroke patients, with durations of 2 to 24 weeks post-stroke, were enrolled in the study. Participants were randomly allocated in a 1:1:1:1 ratio to four groups: the VR group (n = 34), the rTMS group (n = 34), the combined treatment group receiving both VR and rTMS (n = 34), and the control group undergoing traditional balance training (n = 34). All patients underwent a standardized inpatient rehabilitation program over 4 weeks. The VR group received daily 30-min sessions of VR therapy for 20 days. The rTMS group underwent daily sessions of rTMS stimulation for 20 min, targeting the motor imagery region in the affected hemisphere. The combination group received VR therapy after completing their rTMS treatment. The control group received conventional balance training, with each session lasting 30 min. Additionally, all patients received an extra 60 min of standard rehabilitation therapy twice daily. Assessments were conducted at baseline, 2 weeks, and 4 weeks post-treatment, using the Berg Balance Scale (BBS) as the primary measure, and secondary measures including the Timed Up-and-Go Test (TUGT), Fugl-Meyer Assessment-Lower Extremity (FMA-LE), and 6-m walking test (6MWT), as well as assessments for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VGEF), tyrosine receptor kinase (TrκB), motor-evoked potential latency (PL), central motor conduction time (CMCT), and amplitude. Discussion: The widespread application of VR technology and rTMS in clinical settings is well-established. However, the potential synergistic effects of combining these modalities on balance function and neuroplasticity in stroke patients remain uncertain. Our hypothesis suggests that the integration of VR with rTMS may result in more pronounced improvements in both balance function and neuroplasticity among stroke patients, surpassing the outcomes achievable with VR alone, rTMS alone, or traditional therapy. The possible mechanism is that VR-based training combined with rTMS plays a superimposed effect, promoting better repair of damaged neurons and ultimately improving balance function in stroke patients. The positive results anticipated from this trial could provide objective evidence advocating for the concurrent use of VR and rTMS in clinical interventions. Trial registration: The study protocol underwent review and approval by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 26, 2024 (No. KYLL-2024–0162). Subsequently, it was registered in the Chinese Clinical Trial Registry on March 11, 2024 (registration number: ChiCTR2400081775). Currently, the study is still ongoing. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric disorders are highly disabling in traumatic brain injury (TBI) patients, and psychopharmacological treatments often fail to adequately mitigate their detrimental effects. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment in neurology and psychiatry, showing potential in treating psychiatric disorders. Objective: This study investigates the efficacy of a novel, dual-site sequential rTMS protocol designed to treat neuropsychiatric symptoms in a TBI patient who was refractory to conventional treatments. Methods: A 34-year-old woman with severe head trauma and complex psychopathology underwent 20 daily sessions of focal-coil rTMS, combining inhibitory stimulation (1 Hz) on the right dorsolateral prefrontal cortex (DLPFC) and excitatory (10 Hz) on the left DLPFC, guided by a neuronavigation system. Psychiatric and neurocognitive assessments were conducted at baseline and at 2, 4, and 8 weeks following the beginning of rTMS treatment. Results: After 2 weeks of treatment, the patient showed decreased impulsivity and obsessive-compulsive symptoms, along with improvements in attention and processing speed. After 4 weeks, impulsivity further declined, though no other significant changes were noted. At 8 weeks, a persistent positive effect was observed, including enhanced positive emotions. Discussion: These findings suggest that guided, alternating neurostimulation of the DLPFC may modulate activity within cortico-striato-thalamo-cortical circuits, providing a promising alternative for managing neuropsychiatric symptoms in TBI patients who are resistant to traditional treatments. [ABSTRACT FROM AUTHOR]

Sleep's crucial role in memory consolidation is well-established, with neuroimaging and sleep stage analysis revealing the intricate processes involved. Sleep deprivation significantly impairs memory performance and the ability to form new memories, highlighting the need for effective countermeasures. This article concludes that while sleep deprivation significantly impairs memory, the emerging insights into the gut-brain axis offer a promising frontier for developing novel interventions that can mitigate these effects. The review discusses various interventions, ranging from pharmaceutical compounds like donepezil, memantine, and tolcapone, to innovative physical therapy techniques such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and transcranial direct current stimulation (tDCS). Additionally, the emerging role of the gut-brain axis in sleep deprivation-induced memory impairment is examined, shedding light on the complex interplay between gut microbiota and cognitive functions. This comprehensive review explores the multifaceted relationship between sleep deprivation and memory impairment, delving into the neurobiological mechanisms underlying these processes and examining potential interventions. [ABSTRACT FROM AUTHOR]

Numerous studies have reported that long-term sports training can affect inhibitory control and induce brain functional alterations. However, the influence of environmental dynamics in sports training on inter-cortical connectivity has not been well studied. In the current study, we used twin-coil transcranial magnetic stimulation to investigate the functional connectivity between dorsolateral prefrontal cortex (DLPFC) and ipsilateral primary motor cortex (M1) during proactive and reactive inhibition in participants with sports skills in dynamic environment (open-skill experts), stable environment (closed-skill experts), and no sports skills (controls). Using a modified stop signal task, proactive inhibition was measured by the response delay effect (RDE), and reactive inhibition was measured by the stop-signal reaction time (SSRT). Intra-hemispheric DLPFC-M1 interactions and single pulse motor-evoked potentials (MEPs) were measured during the task. A stronger inhibitory effect of the DLPFC over M1 was observed during early reactive control stages compared to baseline levels. In addition, this inhibitory effect was pronounced when comparing open-skill experts to non-athlete controls, a relationship that was significantly correlated with superior reactive control performance. Furthermore, DLPFC to M1 influencing direction shifted from late proactive control to reactive control. Behavioral results also demonstrated enhanced proactive control abilities in open-skill experts relative to controls. Such enhancement may be due to the combination of environmental complexity and physical fitness in long-term skill training. [ABSTRACT FROM AUTHOR]

Background: Robotic exoskeletons have changed rehabilitation care available to people after spinal cord injury (SCI). Yet, the current evidence base is insufficient to identify the optimal dose and neurophysiological mechanism of robotic exoskeleton gait training (RGT) as an effective rehabilitation approach. This study will (1) examine whether the frequency of RGT after motor incomplete SCI impacts function and health outcomes, (2) analyze the neuroplastic effects of RGT dose, and (3) evaluate the safety, tolerability, and feasibility of delivering RGT. Methods: We will enroll 144 participants with motor incomplete SCI admitted to inpatient rehabilitation within 6 months of SCI. Participants will be randomized based on injury severity and level into one of 3 RGT frequency groups (high, moderate, low) or none/usual care only. Participants will complete 24 RGT sessions and be assessed at admission and discharge to inpatient rehabilitation, post-RGT intervention, 1-month post-RGT, and 9-month post-SCI. Outcomes include Walking Index for Spinal Cord Injury-II, health outcomes (gait speed, Spinal Cord Independence Measure, pain, fatigue, spasticity, general health, quality of life, physical activity), and motor evoked potential amplitudes obtained using transcranial magnetic stimulation. Discussion: Successful completion of this study will provide an evidence-based intervention, specifically tailored to meet the unique needs of people with SCI, which supports walking recovery; maximizing health, function, and ultimately participation. The intervention will further support widespread clinical implementation of exoskeleton use during acute rehabilitation. Trial registration: ClinicalTrials.gov NCT05218447. Registered on June 23, 2022. [ABSTRACT FROM AUTHOR]

Introduction: Relapsing-Remitting Multiple Sclerosis manifests various motor symptoms including impairments in corticospinal tract integrity, whose symptoms can be assessed using transcranial magnetic stimulation. Several factors, such as exercise and interlimb coordination, can influence the plastic changes in corticospinal tract. Previous work in healthy and chronic stroke survivors showed that the greatest improvement in corticospinal plasticity occurred during in-phase bilateral exercises of the upper limbs. Altered corticospinal plasticity due to bilateral lesions in the central nervous system is common after Multiple Sclerosis, yet the effect of in-phase bilateral exercise on the bilateral corticospinal plasticity in this cohort remains unclear. Our aim was to investigate the effects of in-phase bilateral exercises on central motor conduction time, motor evoked potential amplitude and latency, motor threshold and clinical measures in people with Relapsing-Remitting Multiple Sclerosis. Methods: Five people were randomized and recruited in this single case concurrent multiple baseline design study. The intervention protocol lasted for 12 consecutive weeks (30–60 minutes /session x 3 sessions / week) and included in-phase bilateral upper limb movements, adapted to different sports activities and to functional motor training. To define the functional relation between the intervention and the results, we conducted a visual analysis. If a potential sizeable effect was observed, we subsequently performed a statistical analysis. Results: Results demonstrated bilateral reduction of the motor threshold alongside with improvement of all clinical measures, but not in any other corticospinal plasticity measures. Conclusion: Our preliminary findings suggest that in-phase bilateral exercise affects motor threshold in people with Relapsing-Remitting Multiple Sclerosis. Therefore, this measure could potentially serve as a proxy for detecting corticospinal plasticity in this cohort. However, future studies with larger sample sizes should validate and potentially establish the effect of in-phase bilateral exercise on the corticospinal plasticity and clinical measures in this cohort. Trial registration: Clinical trial registration: ClinicalTrials.gov NCT05367947. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) triggers time‐locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. Here, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared specific TEP peaks and components between studies using distinct methods. Reporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and preprocessing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the "prototypical" TEP waveform following stimulation of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long‐latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP magnitudes. In summary, some aspects of reporting practices could be improved in future TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention tool for the noninvasive modulation of brain activity and behavior in neuroscience research and clinical settings. However, the resting‐state dynamic evolution of large‐scale functional brain networks following rTMS has rarely been investigated. Here, using resting‐state fMRI images collected from 23 healthy individuals before (baseline) and after 1 Hz rTMS of the left frontal (FRO) and occipital (OCC) lobes, we examined the different effects of rTMS on brain dynamics across the human cortex. By fitting a pairwise maximum entropy model (pMEM), we constructed an energy landscape for the baseline and poststimulus conditions by fitting a pMEM. We defined dominant brain states (local minima) in the energy landscape with synergistic activation and deactivation patterns of large‐scale functional networks. We calculated state dynamics including appearance probability, transitions and duration. The results showed that 1 Hz rTMS induced increased and decreased state probability, transitions and duration when delivered to the FRO and OCC targets, respectively. Most importantly, the shortest path and minimum cost between dominant brain states were altered after stimulation. The absolute sum of the costs from the source states to the destinations was lower after OCC stimulation than after FRO stimulation. In conclusion, our study characterized the dynamic trajectory of state transitions in the energy landscape and suggested that local rTMS can induce significant dynamic perturbation involving stimulated and distant functional networks, which aligns with the modern view of the dynamic and complex brain. Our results suggest low‐dimensional mapping of rTMS‐induced brain adaption, which will contribute to a broader and more effective application of rTMS in clinical settings. [ABSTRACT FROM AUTHOR]

Although significant progress has been made in understanding the cortical correlates underlying balance control, these studies focused on a single task, limiting the ability to generalize the findings. Different balance tasks may elicit cortical activations in the same regions but show different levels of activation because of distinct underlying mechanisms. In this study, twenty young, neurotypical adults were instructed to maintain standing balance while the standing support surface was either translated or rotated. The differences in cortical activations in the frontocentral region between these two widely used tasks were examined using electroencephalography (EEG). Additionally, the study investigated whether transcranial magnetic stimulation could modulate these cortical activations during the platform translation task. Higher delta and lower alpha relative power were found over the frontocentral region during the platform translation task when compared to the platform rotation task, suggesting greater engagement of attentional and sensory integration resources for the former. Continuous theta burst stimulation over the supplementary motor area significantly reduced delta activity in the frontocentral region but did not alter alpha activity during the platform translation task. The results provide a direct comparison of neural activations between two commonly used balance tasks and are expected to lay a strong foundation for designing neurointerventions for balance improvements with effects generalizable across multiple balance scenarios. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively review the effects of repetitive peripheral magnetic stimulation (rPMS) alone or in combination with repetitive transcranial magnetic stimulation (rTMS) on improving upper limb motor functions and activities of daily living (ADL) in patients with stroke, and to explore possible efficacy-related modulators. Methods: A literature search from 1st January 2004 to 1st June 2024 was performed to identified studies that investigated the effects of rPMS on upper limb motor functions and ADL in poststroke patients. Results: Seventeen studies were included. Compared with the control, both rPMS alone or rPMS in combination with rTMS significantly improved upper limb motor function (rPMS: Hedge's g = 0.703, p = 0.015; rPMS + rTMS: Hedge's g = 0.892, p < 0.001) and ADL (rPMS: Hedge's g = 0.923, p = 0.013; rPMS + rTMS: Hedge's g = 0.923, p < 0.001). However, rPMS combined with rTMS was not superior to rTMS alone on improving poststroke upper limb motor function and ADL (Hedge's g = 0.273, p = 0.123). Meta-regression revealed that the total pulses (p = 0.003) and the number of pulses per session of rPMS (p < 0.001) correlated with the effect sizes of ADL. Conclusions: Using rPMS alone or in combination with rTMS appears to effectively improve upper extremity functional recovery and activity independence in patients after stroke. However, a simple combination of these two interventions may not produce additive benefits than the use of rTMS alone. Optimization of rPMS protocols, such as applying appropriate dosage, may lead to a more favourable recovery outcome in poststroke rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a chronic mental illness that affects millions of individuals worldwide. The etiological origin of schizophrenia is heterogeneous, but it has been shown to be associated with dysfunction in serotonin activity, serotonin receptors, and serotonin metabolism in the brain. Bibliometric analysis is a tool used to scrutinise and analyse research activities and evidence in a specific research area. No existing bibliometric analyses have considered both serotonin and schizophrenia. Methods: We conducted a bibliometric analysis including 12,027 studies related to the schizophrenia-serotonin link published from the inception of the study to 2023 and available in the Scopus database. We used VOSviewer software to identify global trends, analyse the author and editors keywords, the most cited articles and author, as well as the most productive institutes and journals publishing research on schizophrenia-serotonin link. Results: Most publications related to the link between schizophrenia and serotonin are focused on adult humans and examine topics such as antipsychotic agents, depression, and serotonin uptake inhibitors. The Journal of Clinical Psychiatry has published the most papers on the schizophrenia-serotonin relationship. Among nations, the United States is the leader in publications. King's College London is the institution with the highest number of publications, and H. Y. Meltzer is the most influential author. Growing trends in schizophrenia-serotonin research are personalised medicine, alternative medicine, transcranial magnetic stimulation, artificial intelligence, nervous system inflammation, brain-gut axis, and the gut microbiome. Conclusion: Since 1950, there have been several fluctuations in the number of published studies related to schizophrenia and serotonin. We believe that the development of novel medications and treatments for schizophrenia will be increased in the future, as well as research into genetic risks, psychological factors, and cranial neuroimaging components. Future schizophrenia and serotonin research is likely to focus on personalised medicine, alternative therapies, novel pathogenesis of schizophrenia, and the use of emerging technologies such as artificial intelligence. [ABSTRACT FROM AUTHOR]

Introduction: Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Methods: Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl- Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. Results: The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA – ipsilateral cerebellum) changes and BBS changes in SMA group. Discussion: In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced c-fos expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices. [ABSTRACT FROM AUTHOR]

A broad spectrum of electromagnetic waves has been explored for wireless neuromodulation. Transcranial magnetic stimulation, with long wavelengths, cannot provide submillimeter spatial resolution. Visible light, with its short wavelengths, suffers from strong scattering in the deep tissue. Microwaves have centimeter-scale penetration depth and have been shown to reversibly inhibit neuronal activity. Yet, microwaves alone do not provide sufficient spatial precision to modulate target neurons without affecting surrounding tissues. Here, we report a split-ring resonator (SRR) that generates an enhanced microwave field at its gap with submillimeter spatial precision. With the SRR, microwaves at dosages below the safe exposure limit are shown to inhibit the firing of neurons within 1 mm of the SRR gap site. The microwave SRR reduced seizure activity at a low dose in both in vitro and in vivo models of epilepsy. This microwave dosage is confirmed to be biosafe via histological and biochemical assessment of brain tissue. [ABSTRACT FROM AUTHOR]

Background/Objectives: Increasing evidence shows an involvement of brain plasticity mechanisms in both motor and central manifestations of neuromuscular disorders (NMDs). These mechanisms could be specifically addressed with neuromodulation or rehabilitation protocols. The aim of this scoping review is to summarise the evidence on plasticity mechanisms' involvement in NMDs to encourage future research. Methods: A scoping review was conducted searching the PubMed and Scopus electronic databases. We selected papers addressing brain plasticity and central nervous system (CNS) studies through non-invasive brain stimulation techniques in myopathies, muscular dystrophies, myositis and spinal muscular atrophy. Results: A total of 49 papers were selected for full-text examination. Regardless of the variety of pathogenetic and clinical characteristics of NMDs, studies show widespread changes in intracortical inhibition mechanisms, as well as disruptions in glutamatergic and GABAergic transmission, resulting in altered brain plasticity. Therapeutic interventions with neurostimulation techniques, despite being conducted only anecdotally or on small samples, show promising results; Conclusions: despite challenges posed by the rarity and heterogeneity of NMDs, recent evidence suggests that synaptic plasticity may play a role in the pathogenesis of various muscular diseases, affecting not only central symptoms but also strength and fatigue. Key questions remain unanswered about the role of plasticity and its potential as a therapeutic target. As disease-modifying therapies advance, understanding CNS involvement in NMDs could lead to more tailored treatments. [ABSTRACT FROM AUTHOR]