The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.

BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1ß in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Effect analysis of repeated transcranial magnetic stimulation combined with fluoxetine in the treatment of first-episode adolescent depression.

Objectives: This study aims to evaluate the efficacy of repeated transcranial magnetic stimulation (rTMS) combined with fluoxetine in enhancing the early antidepressant response in first-episode adolescent depression cases, providing insights for patient diagnosis and treatment. Methods: One hundred and thirty-five adolescents experiencing their first depressive episode were randomly assigned to either a sham group treated with fluoxetine or to low or high repetitive transcranial magnetic stimulation (rTMS) groups receiving both rTMS and fluoxetine. Therapeutic effects were assessed by comparing changes in Hamilton Depression Scale (HAMD-17) scores, cognitive function scores from the Wisconsin Card Sorting Test (WCST), and Clinical Global Impression-improvement (CGI-I) scores, along with recording adverse reactions. Results: The total effectiveness rate in the rTMS groups (Low, 95.56%; High, 97.78%) was significantly higher than in the Sham rTMS group (80%) (F = 11.15, P<0.0001). Post-treatment, not only the Low but also the High rTMS group exhibited more significant reductions in HAMD-17 (Low, 21.05; High, 21.45) and CGI-I scores (Low, 3.44; High, 3.60) compared to the Sham rTMS group (HAMD-17, 16.05; CGI-I, 2.57) (two weeks: F = 7.889, P = 0.0006; four weeks: F = 15.900, P<0.0001). Additionally, the two rTMS groups exhibited fewer erroneous responses and persistent errors in the WCST and completed more WCST categorizations than the Sham rTMS group. There was no significant difference in adverse reaction rates between the groups (F=4.421, P=0.0794). Conclusions: The combination of fluoxetine with rTMS demonstrates enhanced therapeutic effectiveness in treating adolescent depression, effectively controlling disease progression, reducing depressive symptoms, and improving cognitive function, making it a valuable clinical approach.

Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation.

BACKGROUND: Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex. OBJECTIVE: This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS. METHODS: Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data. RESULTS: Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions. CONCLUSION: Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

Explore the durability of repetitive transcranial magnetic stimulation in treating post-traumatic stress disorder: An updated systematic review and meta-analysis.

The objective was to synthesize results from studies that assessed symptom relief after repetitive transcranial magnetic stimulation (rTMS) treatment for post-traumatic stress disorder (PTSD) and investigate the long-term effectiveness of rTMS for treating PTSD. We searched multiple databases for relevant randomized controlled trials of rTMS for PTSD treatment up to 1 January 2023. Two researchers evaluated the studies and focused on the CAPS and PCL as outcome indicators. We used STATA17 SE software for the data analysis. Eight articles involving 309 PTSD patients were analysed in a meta-analysis, which found that rTMS had a significant and large effect on reducing core post-traumatic symptoms [Hedges'g = 1.75, 95% CI (1.18, 2.33)]. Both low and high-frequency rTMS also significantly reduced symptoms, with the latter having a greater effect. rTMS was shown to have a long-term effect on PTSD, with all three subgroup analyses demonstrating significant results. Interestingly, no significant difference in symptom relief was found between the follow-up and completion of treatments [Hedges'g = 0.01, 95% CI (-0.30, 0.33)], suggesting that the treatment effect of rTMS is stable. The meta-analysis provides strong evidence that rTMS is effective in reducing the severity and symptoms of PTSD in patients, and follow-up studies confirm its long-term stability.

Efficacy analysis of three brain stimulation techniques for Alzheimer's disease: a meta-analysis of repeated transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation.

INTRODUCTION: This systematic review and meta-analysis study investigates the efficacy of repeated transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS) using neuropsychological assessments as a potential treatment option for Alzheimer's disease (AD). METHODS: PubMed, Embase, and the Cochrane Library were searched for studies on rTMS, tDCS, and DBS for the treatment of patients with AD between April 1970 and October 2022. The mini-Mental State Examination (MMSE) and AD Assessment Scale - Cognitive Subscale (ADAS-Cog) were adopted as the efficacy index. RESULTS: The analysis yielded 17 eligible studies. rTMS greatly improved the cognition of patients with AD (immediate post-treatment WMD of MMSE score: 2.06, p < 0.00001; short-term follow-up WMD of MMSE score: 2.12, p = 0.006; WMD of ADAS-Cog score in single-arm studies: -4.97, p = 0.001). DBS did not reverse the progression of cognitive decline (WMD of ADAS-Cog score in single-arm studies: 7.40, p < 0.00001). Furthermore, tDCS demonstrated no significant efficacy in improving cognition in random clinical trials or single-arm studies. CONCLUSION: rTMS is a promising non-medicinal alternative for cognitive improvement inpatients with AD.

The cognitive improvement in patients with schizophrenia following low-intensity repetitive transcranial magnetic stimulation could last for 6 months: A randomized controlled trial.

Cognitive impairments are a core symptom of schizophrenia. Although low-intensity repetitive transcranial magnetic stimulation (rTMS) also has cognitive improving effect like the commonly used high-intensity rTMS, it has not been applied in schizophrenia yet. To fill this gap, inpatients with schizophrenia were randomized to receive 20 sessions of daily adjunctive active low-intensity rTMS in 4 weeks, or sham treatment. At baseline, 4 weeks, and 6 months, the Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptom severity, while the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color and Word Test (SCWT) were used to assess cognitive functions. Compared to the sixty-nine patients receiving sham treatment, those fifty-nine patients receiving active rTMS performed better in all cognitive domains at post-treatment with small to large effect sizes. This superiority of active rTMS over sham treatment remained significant at 6-month follow-up, with small to large effect sizes, except for visuospatial function and delayed memory. The reduction in PANSS scores were not correlated with cognitive improvements. Our findings provide evidence for using low-intensity rTMS to ameliorate cognitive impairments in schizophrenia. More research are needed to determine the optimal intensity for each domain of cognitive functions.

Efficacy of repetitive transcranial magnetic stimulation at different sites for peripheral facial paralysis: a prospective cohort study.

Background: There are very few studies on transcranial magnetic stimulation (TMS) therapy for facial paralysis and no studies comparing the efficacy of central and peripheral TMS in the treatment of peripheral facial paralysis (PFP). Purpose: To observe the therapeutic effect and security of central and peripheral repetitive transcranial magnetic stimulation (rTMS) on PFP. Methods: Patients with unilateral onset of peripheral facial paralysis within 1 month were prospectively recruited, 97 patients with PFP were divided into the peripheral group, central group, and control group. The control group was given common treatment (drug therapy and acupuncture), and the peripheral and central groups received rTMS in addition to conventional treatment. After 2 weeks of treatment, the House-Brackmann (HB) grading scale, Sunnybrook facial grading system (SFGS), and modified Portmann scale (MPS) were used to evaluate the facial muscle function of patients in the three groups. Result: After 2 weeks of rTMS treatment, the HBGS/SFGS/MPS scores of the three groups were significantly better than before (p < 0.05), and the mean change values of HBGS, SFGS, and MPS scores were significantly higher in participants in Peripheral Group (p < 0.001; p < 0.001; p = 0.003; respectively) and Central Group (p = 0.004; p = 0.003; p = 0.009; respectively) than in Control Group. But the mean change values of HBGS, SFGS, and MPS scores showed no significant differences in participants in the Peripheral Group than in the Central Group (p = 0.254; p = 0.139; p = 0.736; respectively) after 2 weeks of treatment (p > 0.05). Conclusion: Our study shows that rTMS can be a safe and effective adjuvant therapy for patients with PFP. Preliminary studies have shown that both peripheral and central stimulation can effectively improve facial nerve function, but there is no significant difference in the efficacy of the two sites.

Effects of Repetitive Transcranial Magnetic Stimulation at the Cerebellum on Working Memory.

Transcranial magnetic stimulation is a widely used brain intervention technique in clinical settings. In recent years, the role of the cerebellum in learning and memory has become one of the hotspots in the field of cognitive neuroscience. In this study, we recruited 36 healthy college or graduate students as subjects and divided them into groups, with 10 to 14 subjects in each group. We performed 5 Hz and 20 Hz repeated transcranial magnetic stimulation and sham stimulation on the Crus II subregion of the cerebellum in different groups, then let them complete the 2-back working memory task before and after the stimulation. We simultaneously recorded the electroencephalogram in the experiment and analyzed the data. We found that after repeated transcranial magnetic stimulation of the cerebellum at 5 Hz and 20 Hz, the N170 and P300 event-related potential components in the prefrontal cortex showed significant differences compared to those in the sham stimulation group. Using phase-locked values to construct brain networks and conduct further analysis, we discovered that stimulation frequencies of 5 Hz and 20 Hz had significant effects on the local and global efficiency of brain networks in comparison to the sham stimulation group. The results showed that repeated transcranial magnetic stimulation on cerebellar targets can effectively affect the subjects' working memory tasks. Repeated transcranial magnetic stimulation at 5 Hz and 20 Hz could enhance the excitatory responses of the frontal lobes. After stimulation at 5 Hz and 20 Hz, the efficiency of the brain network significantly improved.

The repetitive transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: a case report.

BACKGROUND: Repetitive transcranial magnetic stimulation is a noninvasive intervention, can significantly reduce behavioral and psychological symptoms and cognitive impairment in AD patients. Only few cases have been reported the adverse reactions after the treatment. This report described the different adverse reactions after repetitive transcranial magnetic stimulation with different parameters. PATIENT PRESENTATION: This article reports a patient with dementia complicated with mental behavior disorder who was treated with repetitive transcranial magnetic stimulation (rTMS) in spite of poor drug response. First, 1 Hz rTMS was initiated. After 1 month, the patient showed improved symptoms of mental behavior, decreased cognitive function and prolonged sleep duration. After switched to 10 Hz rTMS, the patient's cognitive function and mental behavior abnormalities improved, and the sleep time returned to normal. However, epilepsy occurred after one session and was changed to 0.8 Hz rTMS treatment. The patient's symptoms improved and did not have seizure. CONCLUSION: Repetitive transcranial magnetic stimulation has a positive effect on cognitive function and Behavioral And Psychological Symptoms Of Dementia, and adverse reactions are inevitable. Playing personalized treatment according to the patients can reduce occurrence of adverse reactions.

rTMS treatment for abrogating intracerebral hemorrhage-induced brain parenchymal metabolite clearance dysfunction in male mice by regulating intracranial lymphatic drainage.

BACKGROUND: The discovery of the glymphatic system and meningeal lymphatic vessels challenged the traditional view regarding the lack of a lymphatic system in the central nervous system. It is now known that the intracranial lymphatic system plays an important role in fluid transport, macromolecule uptake, and immune cell trafficking. Studies have also shown that the function of the intracranial lymphatic system is significantly associated with neurological diseases; for example, an impaired intracranial lymphatic system can lead to Tau deposition and an increased lymphocyte count in the brain tissue of mice with subarachnoid hemorrhage. METHODS: In this study, we assessed the changes in the intracranial lymphatic system after intracerebral hemorrhage and the regulatory effects of repeated transcranial magnetic stimulation on the glymphatic system and meningeal lymphatic vessels in an intracerebral hemorrhage (ICH) model of male mice. Experimental mice were divided into three groups: Sham, ICH, and ICH + repeated transcranial magnetic stimulation (rTMS). Three days after ICH, mice in the ICH+rTMS group were subjected to rTMS daily for 7 days. Thereafter, the function of the intracranial lymphatic system, clearance of RITC-dextran and FITC-dextran, and neurological functions were evaluated. RESULTS: Compared with the Sham group, the ICH group had an impaired glymphatic system. Importantly, rTMS treatment could improve intracranial lymphatic system function as well as behavioral functions and enhance the clearance of parenchymal RITC-dextran and FITC-dextran after ICH. CONCLUSION: Our results indicate that rTMS can abrogate ICH-induced brain parenchymal metabolite clearance dysfunction by regulating intracranial lymphatic drainage.

[Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial].

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION: Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

Efficacy and safety of repeated transcranial magnetic stimulation combined with escitalopram in the treatment of major depressive disorder: a meta-analysis.

Objective: This study was designed to systematically review the efficacy and safety of repeated transcranial magnetic stimulation (rTMS) combined with escitalopram in treating major depressive disorder (MDD). Methods: Databases including PubMed, Embase, Cochrane, Web of Science, CNKI, Wanfang, VIP Journal, and China Biomedical Literature databases were electronically searched for randomized controlled trials of rTMS combined with escitalopram intervention for MDD treatment from the inception of these databases to 27 May 2023. Two reviewers independently screened the studies, extracted the data, and assessed the quality of the included studies. R 4.2.2 was then used for a meta-analysis. Results: In total, 19 articles involving 1,032 patients were included. The results of the meta-analysis showed that Hamilton Depression Rating Scale (HAMD) scores were significantly lower in the group receiving rTMS combined with escitalopram (experimental group) than that in the control group [weighted mean difference (WMD) = -5.30, 95% confidence interval (95% CI): -6.44 to -4.17, p < 0.01]. The response rate of the experimental group was significantly higher than that of the control group [odds ratio (OR): 5.48; 95% CI: 3.72 to 8.07; p < 0.01]. No significant difference in the adverse reaction rate was observed between the two groups (OR: 1.04, 95% CI: 0.71 to 1.52, p = 0.82). Conclusion: Our findings suggest that rTMS combined with escitalopram can benefit patients with MDD in a safe manner, which may help in guiding clinical practice. Systematic review registration: DOI number: 10.37766/inplasy2023.11.0114, INPLASY2023110114.

Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism.@*METHODS@#A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05).@*CONCLUSION@#Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder and Tic Disorder: A Quick Review.

Repetitive transcranial megnetic stimulation (rTMS) has been widely used in patients with psychiatric disorders. Previous studies revealed good efficacy of rTMS for patients with obsession-compulsive disorder (OCD) and Tic disorder (TD). OCD and TD are closely related and considered to etiologically overlap. Patients with the co-occurrence of OCD and TD are often identified. Therefore, we conducted a quick review of rTMS for the treatment of these two diseases to compare the similarities and differences of rTMS for OCD and TD, which might provide an indication for the treatment of the co-occurrence of OCD and TD. We searched articles published in PubMed, Wanfang, and Web of Science from January 2001 to January 2022. Both inclusion criteria and exclusion criteria were developed to identify the relevant included studies. Data on the frequency, target area, sample size, and number of males, especially the rTMS treatment procedure or parameters, were extracted in the included studies. We included 26 studies on OCD and 12 studies on TD in this quick review. A total of 996 participants were included. Based on the review of the included studies, lowfrequency rTMS might be used more than high-frequency rTMS, and the supplementary motor area (SMA) might show better efficacy than the dorsolateral prefrontal cortex (DLPFC) in OCD. For patients with TD, low-frequency rTMS located in the SMA might show good efficacy both in OCD and TD. Our quick review elaborated the treatment efficacy of rTMS for both patients with OCD and those with TD. It seems that the SMA is an important target choice for both OCD and TD patients. Low-frequency rTMS might be used more than high-frequency rTMS in both OCD and TD patients. In future studies, we should explore more about the efficacy of rTMS for patients with co-occurring OCD and TD, especially for the efficacy of targeted SMA with low frequency.

Integrative medicine in treating post-stroke depression: Study protocol for a multicenter, prospective, randomized, controlled trial.

Background: Post-stroke depression (PSD) is one of the most common neuropsychiatric diseases in patients with stroke, and it can increase the disability rate, mortality, and recurrence rate of stroke. Currently, many clinical studies have indicated that traditional Chinese medicine (TCM), such as acupuncture and herbs, Western medicine, rehabilitation, repeated transcranial magnetic stimulation, and other treatment methods, are effective in treating PSD. However, no study has formulated a comprehensive treatment plan that integrates TCM, Western medicine, and rehabilitation for PSD. Thus, this trial aims to assess the efficacy and safety of integrative medicine for treating PSD. Methods: This multicenter, prospective, randomized, controlled study aims to form a set of effective clinical treatment schemes that integrate TCM, Western medicine, and rehabilitation for PSD. A total of 202 participants recruited from four centers will be randomized into either the integrative medicine or standard care group. Standard care-basic treatment, general nursing care, and exercise therapy-will be provided to all participants. The integrative medicine group will also receive acupuncture, Chinese herbs, and repeated transcranial magnetic stimulation (rTMS). Participants will receive acupuncture and rTMS treatments five times per week for 4 weeks and will be administered Chinese herbs, basic treatment, general nursing care, and exercise therapy for 4 weeks. The primary outcomes include the Hamilton Depression Scale (HAMD), Self-Rating Depression Scale (SDS), and Activity of Daily Living Scale (ADL). And the secondary outcomes include the Montreal Cognitive Assessment Scale, the Fugl-Meyer Assessment (FMA) Scale, and the Pittsburgh Sleep Quality Index (PSQI). All outcome measures will be evaluated at baseline, week 4 (the end of the treatment courses), and week 8 (the end of follow-up). Safety assessments will be performed throughout the study. Discussion: This study is expected to verify the efficacy and safety of integrative medicine for treating PSD, providing an evidence-based clinical reference for the future development of a standardized scheme. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05187975.

The Efficacy of Integrated Rehabilitation for Post-Stroke Anxiety: Study Protocol for a Prospective, Multicenter, Randomized Controlled Trial.

Background: Post-stroke anxiety (PSA) remains a challenging medical problem. Integrated rehabilitation involves a combination of traditional Chinese medicine (TCM) and Western conventional rehabilitation techniques. Theoretically, integrated rehabilitation is likely to have significant advantages in treating PSA. Nevertheless, the therapeutic effect of integrated rehabilitation needs to be verified based on large-scale trials with sound methodology. Thus, the aim of this trial is to assess the efficacy and safety of integrated rehabilitation on PSA. Methods: The study is a prospective, multicenter, randomized, controlled trial involving 188 PSA patients from four clinical centers in China. Eligible participants will be randomly divided into the integrated rehabilitation group or the standard care group. Participants in the integrated rehabilitation group will receive a combination of TCM and Western conventional rehabilitation methods, including acupuncture, repeated transcranial magnetic stimulation, traditional Chinese herbal medicine, and standard care. The primary outcome will be the Hamilton Anxiety Rating Scale (HAM-A). The secondary outcomes will include the Self-Rating Anxiety Scale (SAS), the Activities of Daily Living (ADL) scale, the Montreal Cognitive Assessment (MoCA) scale, the simplified Fugl-Meyer Assessment of motor function (FMA) scale, and the Pittsburgh Sleep Quality Index (PSQI). Outcome measurements will be performed at baseline, at the end of the 4-week treatment and the 8-week follow-up. Conclusion: Results of this trial will ascertain the efficacy and safety of integrated rehabilitation on PSA, thereby providing evidence regarding integrated rehabilitation strategies for treating PSA. It will also promote up-to-date evidence for patients, clinicians, and policy-makers. Trial Registration: ClinicalTrials.gov NCT05147077.

Hemodynamic signal changes and swallowing improvement of repetitive transcranial magnetic stimulation on stroke patients with dysphagia: A randomized controlled study.

Objective: Our study aims to measure the cortical correlates of swallowing execution in patients with dysphagia after repetitive transcranial magnetic stimulation (rTMS) therapy using functional near-infrared spectroscopy (fNIRS), and observe the change of pattern of brain activation in stroke patients with dysphagia after rTMS intervention. In addition, we tried to analyze the effect of rTMS on brain activation in dysphagia patients with different lesion sides. This study also concentrated on the effect of stimulating the affected mylohyoid cortical region by 5 Hz rTMS, providing clinical evidence for rTMS therapy of dysphagia in stroke patients. Methods: This study was a sham-controlled, single-blind, randomized controlled study with a blinded observer. A total of 49 patients completed the study, which was randomized to the rTMS group (n = 23) and sham rTMS group (n = 26) by the random number table method. The rTMS group received 5 Hz rTMS stimulation to the affected mylohyoid cortical region of the brain and the sham rTMS group underwent rTMS using the same parameters as the rTMS group, except for the position of the coil. Each patient received 2 weeks of stimulation followed by conventional swallowing therapy. Standardized Swallowing Assessment (SSA), Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), Penetration-Aspiration Scale (PAS), and functional oral intake status were assessed at two times: baseline (before treatment) and 2 weeks (after intervention). Meanwhile, we use the fNIRS system to measure the cerebral hemodynamic changes during the experimental procedure. Results: The rTMS group exhibited significant improvement in the SSA scale, FEDSS scale, and PAS scale after rTMS therapy (all P < 0.001). The sham rTMS group had the same analysis on the same scales (all P < 0.001). There was no significant difference observed in clinical assessments at 2 weeks after baseline between the rTMS group and sham rTMS group (all P > 0.05). However, there were statistically significant differences between the two groups in the rate of change in the FEDSS score (P = 0.018) and PAS score (P = 0.004), except for the SSA score (P = 0.067). As for the removal rate of the feeding tube, there was no significant difference between the rTMS group and sham rTMS group (P = 0.355), but there was a significant difference compared with the baseline characteristics in both groups (P rTMS < 0.001, P shamrTMS = 0.002). In fNIRS analysis, the block average result showed differences in brain areas RPFC (right prefrontal cortex) and RMC (right motor cortex) significantly between the rTMS group and sham rTMS group after intervention (P channel30 = 0.046, P channel16 = 0.006). In the subgroup analysis, rTMS group was divided into left-rTMS group and right-rTMS group and sham rTMS group was divided into sham left-rTMS group and sham right-rTMS group. The fNIRS results showed no significance in block average and block differential after intervention between the left-rTMS group and sham left-rTMS group, but differences were statistically significant between the right-rTMS group and sham right-rTMS group in block average: channel 30 (T = -2.34, P = 0.028) in LPFC (left prefrontal cortex) and 16 (T = 2.54, P = 0.018) in RMC. After intervention, there was no significance in left-rTMS group compared with baseline, but in right-rTMS group, channel 27 (T = 2.18, P = 0.039) in LPFC and 47 (T = 2.17, P = 0.039) in RPFC had significance in block differential. In the sham rTMS group, neither sham left-rTMS group and sham right-rTMS group had significant differences in block average and block differential in each brain area after intervention (P > 0.05). Conclusions: The present study confirmed that a 5-Hz rTMS is feasible at the affected mylohyoid cortical region in post-stroke patients with dysphagia and rTMS therapy can alter cortical excitability. Based on previous studies, there is a dominant hemisphere in swallowing and the results of our fNIRS analysis seemed to show a better increase in cortical activation on the right side than on the left after rTMS of the affected mylohyoid cortical region. However, there was no difference between the left and right hemispheres in the subgroup analysis. Nevertheless, the present study provides a novel and feasible method of applying fNIRS to assessment in stroke patients with dysphagia.

Combining Trauma Script Exposure With rTMS to Reduce Symptoms of Post-Traumatic Stress Disorder: Randomized Controlled Trial.

BACKGROUND: Innovative therapeutic interventions for post-traumatic stress disorder (PTSD) are required. We opted to facilitate fear extinction by combining trauma script exposure with repetitive transcranial magnetic stimulation (rTMS) to reduce symptoms of PTSD. OBJECTIVE: The efficacy and safety of 10 Hz rTMS of the right dorsolateral prefrontal cortex simultaneously with exposure to personal traumatic narrative were studied in patients with PTSD. MATERIALS AND METHODS: This trial was a single-center randomized controlled trial (NCT02584894). Patients were randomly assigned 1:1 to receive eight daily sessions of 110% of motor threshold high frequency (HF) 10 Hz rTMS (110% HF rTMS) or 70% low frequency (LF) 1 Hz rTMS (70% LF rTMS) with trauma script exposure in both groups. Severity of PTSD, depression, and anxiety were assessed before and after study treatment (one month, three months) by an assessor masked to the trial group assignment. The primary outcome was the severity of PTSD assessed by the Clinician Administered PTSD Scale (CAPS). We used mixed linear regression models for statistical comparisons. RESULTS: Thirty-eight patients (65.8% females) were randomly assigned to 110% HF rTMS (n = 18, 31.3 ± 10.0 years, 13 females) or 70% LF rTMS (n = 20, 33.5 ± 11.1 years, 12 females). From baseline to three months, mean CAPS scores decreased by 51% in the 110% HF rTMS group (from 83.7 ± 14.4 to 41.8 ± 31.9) and by 36.9% in the 70% LF rTMS group (from 81.8 ± 15.6 to 51.6 ± 23.7), but with no significant difference in improvement (time by treatment interaction -3.61 [95% confidence interval (CI), -9.70 to 2.47]; p = 0.24; effect size 0.53). One serious adverse event occurred during the study (psychogenic nonepileptic seizure). CONCLUSION: We found no evidence of difference in clinical improvement or remission rates between the 110% HF and 70% LF stimulation. These findings may reflect the importance of exposure procedure and that larger number of participants is needed.

Effects of Noninvasive Brain Stimulation Combined With Antidepressants in Patients With Poststroke Depression: A Systematic Review and Meta-Analysis.

Objective: To evaluated the efficacy and safety of noninvasive brain stimulation (NIBS) combined with antidepressants in patients with poststroke depression (PSD). Methods: Seven databases were searched to identify randomized controlled trials of NIBS combined with antidepressants in the treatment of PSD based on the international classification of diseases (ICD-10) criteria and exclusion criteria. The retrieval time was from the database establishment to 31 October 2021. Two researchers independently screened the identified studies through the search strategy, extracted their characteristics, and evaluated the quality of the included literature. Cochrane Collaboration's tool was used to assess risk of bias. RevMan 5.3 software was applied for meta-analysis. Results: A total of 34 randomized controlled trials were included, involving 2,711 patients with PSD. Meta-analysis showed that the total effective rate was higher in the combined therapy than the antidepressant alone [odds ratio (OR): 4.33; 95% confidence interval (CI): 3.07 to 6.11; p < 0.00001]. The Hamilton depressive scale (HAMD) score was significantly lower in repeated transcranial magnetic stimulation (rTMS) (≤10 Hz) combined with antidepressant than in antidepressant alone [standard mean difference (SMD): -1.44; 95% CI: -1.86 to -1.03; p < 0.00001]. No significant difference was seen in rTMS (>10 Hz) combined with antidepressant versus antidepressant alone (SMD: -4.02; 95% CI: -10.43 to 2.39; p = 0.22). In addition, combination therapy more strongly improved the modified Barthel index (MBI) scale than antidepressants [mean difference (MD): 8.29; 95% CI: 5.23-11.35; p < 0.00001]. Adverse effects were not significantly different between two therapies (OR: 1.33; 95% CI: 0.87 to 2.04; p = 0.18). Conclusion: Low-frequency rTMS (≤10 Hz) combined with antidepressants tends to be more effective than antidepressants alone in patients with PSD, and there are no significant adverse effects. In addition, combined therapy may enhance quality of life after stroke. Combination therapy with high-frequency rTMS (>10 Hz) showed no advantage in treating PSD. The transcranial electrical stimulation (TES) combined with antidepressants might be more effective than antidepressants alone, which are needed to confirm by more clinical trials since the.

Low-frequency rTMS treatment alters the topographical organization of functional brain networks in schizophrenia patients with auditory verbal hallucination.

Auditory verbal hallucinations (AVH) are an important characteristic of schizophrenia. Repeated transcranial magnetic stimulation (rTMS) has been evidence to be effective in treating AVH. We evaluated the topological properties of resting-state functional brain networks in schizophrenia patients with AVH (n = 32) who received 1-Hz rTMS treatment and matched healthy controls (n = 33). The results showed that the psychotic symptoms and certain neurocognitive performances in patients were improved by rTMS treatment. Furthermore, the pretreatment patients showed abnormal global topological metrics compared with the controls, including lower global efficiency (Eglob, represents the relative quality of information transmission between all nodes in the network) and higher characteristic path length (Lp, characterizes the mean shortest distance between any two nodes in the network). The pretreament patients also showed decreased local topological metrics relative to the controls, including the nodal shortest path (NLp, quantifies the mean distance between the given node and the other nodes in the network) and nodal efficiency (Ne, measures the information interchange among the neighbor nodes when one node is removed), mainly located in the prefrontal cortex, occipital cortex, and subcortical regions. While the abnormal global and local topological patterns were normalized in patients after rTMS treatment. The multiple linear regression analysis indicated that the baseline topological metrics could be associated with the clinical responses after treatment in the patient group. The results suggested that the topological organization of the functional brain network was globally and regionally altered in schizophrenia patients with AVH after rTMS treatment and may be a potential therapeutic effect for AVH in schizophrenia.