Stroke is a major cause of adult disability worldwide, often involving disruption of the blood-brain barrier (BBB). Repairing the BBB is crucial for stroke recovery, and pericytes, essential components of the BBB, are potential intervention targets. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for functional impairments after stroke, with potential effects on BBB integrity. However, the underlying mechanisms remain unclear. In this study using a transient middle cerebral artery occlusion (tMCAO) rat model, we investigated the impact of rTMS on post-stroke BBB. Through single-cell sequencing (ScRNAs), we observed developmental relationships among pericytes, endothelial cells, and vascular smooth muscle cells, suggesting the differentiation potential of pericytes. A distinct subcluster of pericytes emerged as a potential therapeutic target for stroke. Additionally, our results revealed enhanced cellular communication among these cell types, enriching signaling pathways such as IGF, TNF, NOTCH, and ICAM. Analysis of differentially expressed genes highlighted processes related to stress, differentiation, and development. Notably, rTMS intervention upregulated Reck in vascular smooth muscle cells, implicating its role in the classical Wnt signaling pathway. Overall, our bioinformatics findings suggest that rTMS may modulate BBB permeability and promote vascular regeneration following stroke. This might happen through 20 Hz rTMS promoting pericyte differentiation into vascular smooth muscle cells, upregulating Reck, then activating the classical Wnt signaling pathway, and facilitating vascular regeneration and BBB stability.

Aims/Background High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and intermittent theta burst stimulation (iTBS) are emerging neuromodulation techniques for major depressive disorder (MDD). However, clinical trials directly comparing their efficacy are limited. This meta-analysis aimed to evaluate the antidepressant effects and safety profiles of iTBS versus HF-rTMS for MDD. Methods A systematic literature search was conducted in major databases to identify randomized controlled trials (RCTs) comparing iTBS and HF-rTMS for MDD. The primary outcome measures were response rate, remission rate, and common side effects. Meta-analysis was performed using fixed-effects and random-effects models. Publication bias was assessed. Results Seven RCTs were included in the meta-analysis. No significant differences were found in response rate (odds ratio (OR) 0.97, 95% confidence interval (95% CI) 0.81 to 1.16, p = 0.75) or remission rate (OR 1.06, 95% CI 0.85 to 1.31, p = 0.62) between iTBS and HF-rTMS. Both active stimulations showed significantly higher response rates than sham treatment. The odds of response were 4-5 times greater for iTBS versus sham (OR 4.84, 95% CI 2.66 to 8.80, p < 0.001) and 3-4 times greater for HF-rTMS versus sham (OR 3.85, 95% CI 2.08 to 7.13, p < 0.001). No differences in common side effects such as headache were observed between iTBS and HF-rTMS. Conclusion iTBS and HF-rTMS have comparable efficacy and safety profiles in treating MDD based on current evidence. Both neuromodulation techniques are superior to sham stimulation. iTBS could be considered an alternative to HF-rTMS, with the advantage of shorter daily treatment duration. Further large RCTs with long-term follow-up are warranted to confirm these findings.

OBJECTIVE: To assess the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation in the prevention or treatment of migraine by conducting a pooled analysis of relevant randomized controlled trials.
METHODS: The PubMed, Embase, Cochrane, OVID, SCOPUS, Web of Science, and clinicaltrials.gov databases were systematically searched for randomized controlled trials (RCTs) comparing high-frequency rTMS and sham stimulation for the prevention or treatment of migraine. A meta-analysis of relevant outcome measures was performed using RevMan 5.3 software.
RESULTS: Eight RCTs with a total of 384 patients were included. A total of 23 patients dropped out, and thus, 361 patients were ultimately included for analysis. The high-frequency rTMS group had a lower frequency of attacks than the sham group (MD = - 5.10; 95% CI: - 8.10, - 2.09; P = 0.0009). The rTMS group has less intense headaches than the sham group (SMD = - 0.74; 95% CI - 1.04, - 0.44; P < 0.00001). High-frequency rTMS improved patient disability (SMD = - 0.45; 95% CI - 0.75, - 0.16; P = 0.003). High-frequency rTMS led to no advantage in reducing the number of abortive medications (MD = - 1.10; 95% CI - 3.28, 1.08; P = 0.32), but it increased the occurrence of adverse events (RR = 1.69; 95% CI 1.09, 2.64; P = 0.02).
CONCLUSIONS: High-frequency rTMS reduces the frequency of attacks and headache intensity in migraine patients and improves the patient\'s disability, but it also increases adverse events.

UNASSIGNED: To investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with galantamine in patients with cognitive impairment after stroke and its effect on serum homocysteine (Hcy) and neuron-specific enolase (NSE) levels.
UNASSIGNED: A total of 90 patients with cognitive impairment after the first ischemic stroke were enrolled. They were randomly divided into rTMS+ cognitive rehabilitation group, Galantamine + cognitive rehabilitation group, and rTMS+ Galantamine + cognitive rehabilitation group. All groups received routine medical treatment and limb rehabilitation treatment. The rTMS stimulation site was the left dorsolateral prefrontal cortex (left DLPFC), the magnetic stimulation frequency was 5 Hz, the magnetic stimulation intensity was 80% of the motor threshold level, and 3,000 pulses were given every day. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fugl-Meyer scale, and modified Barthel index, as well as rehabilitation scale and serum NSE and Hcy were evaluated before and after treatment (after 4 weeks).
UNASSIGNED: After 4 weeks of treatment, the scores of MMSE, MoCa scale, Fugl-Meyer scale, and modified Barthel index in the three groups were significantly higher than those before treatment (all p < 0.05), while the serum NSE and Hcy levels of the three groups were decreased. rTMS+ Galantamine + cognitive rehabilitation group had higher scale scores, and the difference between the three groups was statistically significant compared with the other two groups (all p < 0.05).
UNASSIGNED: Cognitive rehabilitation combined with HF-rTMS and galantamine could improve the cognitive function of patients to the greatest extent, promote the recovery of physical activity, improve the self-care ability of daily life, and effectively reduce the serum HCY and NSE levels in patients with cognitive impairment after stroke. No randomized controlled trials of similar combination treatments have been reported. The better therapeutic effect may be related to the fact that galantamine combined with repetitive transcranial magnetism can activate the brain cholinergic system more extensively, promote brain neural remodeling through long-term potentiation and inhibit local neuroinflammatory responses in brain injury.

BACKGROUND: Post-stroke dysphagia (PSD) is a common symptom of stroke. Clinical complications of PSD include malnutrition and pneumonia. Clinical studies have shown that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) can improve the swallowing function in stroke patients. However, few studies have elucidated the underlying molecular mechanisms.
METHODS: A PSD rat model was established using transient middle cerebral artery occlusion (tMCAO). Rats were randomly divided into sham-operated groups, PSD groups, PSD + sham-rTMS groups, PSD + 5 Hz-rTMS groups, PSD + 10 Hz-rTMS groups and PSD + 20 Hz-rTMS groups. Rats were weighed and videofluoroscopic swallowing studies were conducted. Pulmonary inflammation, levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in the serum, lung, and nucleus tractus solitarius (NTS), brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine (5HT) in NTS were evaluated.
RESULTS: Rats in the PSD group experienced weight loss, reduced bolus area and pharyngeal bolus speed, and increased pharyngeal transit time (PTT) and inter-swallow interval (ISI) on day 7 and day 14 after operation. Moreover, PSD rats showed pulmonary inflammation, reduced levels of SP in the lung and serum, increased levels of CGRP in the lung and NTS, reduced levels of BDNF and 5HT in the NTS. There was no significant difference between the PSD group and the PSD + sham-rTMS group in the results of weight and VFSS. Comparing with the PSD group, there significant increases in the bolus area, decreases in PTT of rats following 5 Hz rTMS intervention. HF-rTMS at 10 Hz significantly increased the weight, bolus area, pharyngeal bolus speed and decreased the PTT and ISI of rats. There were also significant increases in the bolus area (p < 0.01) and pharyngeal bolus speed, decreases in PTT and ISI of rats following 20 Hz rTMS intervention. Furthermore, compared with the PSD + 5 Hz-rTMS group, there were significant increases in the bolus area and pharyngeal bolus speed, decreases in ISI in the swallowing function of rats in the PSD + 10 Hz-rTMS group. Besides, compared with the PSD + 5 Hz-rTMS group, there were significant decreases in ISI in the swallowing function of rats in the PSD + 20 Hz-rTMS group. HF-rTMS at 10 Hz alleviated pulmonary inflammation, increased the levels of SP in the lung, serum, and NTS, CGRP in the serum and NTS, 5HT in the NTS of PSD rats.
CONCLUSIONS: Compared with 5 Hz and 20 Hz rTMS, 10 Hz rTMS more effectively improved the swallowing function of rats with PSD. HF-rTMS at 10 Hz improved the swallowing function and alleviated pneumonia in PSD rats. The mechanism may be related to increased levels of SP in the lung, serum and NTS, levels of CGRP in the serum and NTS, 5HT in the NTS after HF-rTMS treatment.

OBJECTIVE: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC).
METHODS: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses.
RESULTS: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56-0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R2 =0.53) and age(R2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15-20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15-1.10) when combining all doses.
CONCLUSIONS: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy.

Treatment-resistant depression (TRD) poses significant therapeutic challenges despite available interventions. Escitalopram (ESC) is a highly selective antidepressant. This study aimed to compare ESC alone and ESC combined with modified electroconvulsive therapy (MECT) or high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in TRD patients. Ninety participants were randomized into ESC alone, ESC + MECT, and ESC + HF-rTMS groups. Notable differences were observed in Hamilton Depression Rating Scale (HDRS-17) scores at 12 weeks among ESC (14.37), ESC + MECT (10.27), and ESC + HF-rTMS (10.77) groups (P = 0.006). In terms of overall quality of life (QoL) evaluated using the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) at 12 weeks, the ESC, ESC + MECT, and ESC + HF-rTMS groups scored 2, 3, and 3.5, respectively. ESC + MECT/HF-rTMS groups showed reduced depressive symptoms compared to the ESC group, accompanied by higher overall QoL scores and increased satisfaction with health. Patients receiving ESC + MECT demonstrated no significant alterations in short-term memory and orientation, as measured by the Montreal Cognitive Assessment (MoCA), before and after treatment. Moreover, a decline in language was observed compared to baseline (12 weeks: median 2, IQR 2-3; baseline: median 1, IQR 1-3; P = 0.022). The positive impact of ESC with HF-rTMS on cognitive function was evidenced by improvements in all domines MoCA.Combining ESC with MECT or HF-rTMS exhibited enhanced effectiveness in alleviating depressive symptoms and enhancing QoL compared to ESC monotherapy. Specifically, the ESC + HF-rTMS combination displayed potential as a comprehensive treatment strategy for TRD, addressing both emotional and cognitive aspects.

Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.

UNASSIGNED: It has been proved that repetitive transcranial magnetic stimulation (rTMS) triggers the modulation of homeostatic metaplasticity, which causes the effect of rTMS to disappear or even reverse, and a certain length of interval between rTMS trains might break the modulation of homeostatic metaplasticity. However, it remains unknown whether the effects of high-frequency rTMS can be modulated by homeostatic metaplasticity by lengthening the train duration and whether homeostatic metaplasticity can be broken by prolonging the inter-train interval.
UNASSIGNED: In this study, 15 subjects participated in two experiments including different rTMS protocols targeting the motor cortex. In the first experiment, high-frequency rTMS protocols with different train durations (2 s and 5 s) and an inter-train interval of 25 s were adopted. In the second experiment, high-frequency rTMS protocols with a train duration of 5 s and different inter-train intervals (50 s and 100 s) were adopted. A sham protocol was also included. Changes of motor evoked potential amplitude acquired from electromyography, power spectral density, and intra-region and inter-region functional connectivity acquired from electroencephalography in the resting state before and after each rTMS protocol were evaluated.
UNASSIGNED: High-frequency rTMS with 2 s train duration and 25 s inter-train interval increased cortex excitability and the power spectral density of bilateral central regions in the alpha frequency band and enhanced the functional connectivity between central regions and other brain regions. When the train duration was prolonged to 5 s, the after-effects of high-frequency rTMS disappeared. The after-effects of rTMS with 5 s train duration and 100 s inter-train interval were the same as those of rTMS with 2 s train duration and 25 s inter-train interval.
UNASSIGNED: Our results indicated that train duration and inter-train interval could induce the homeostatic metaplasticiy and determine the direction of intensity of rTMS after-effects, and should certainly be taken into account when performing rTMS in both research and clinical practice.

UNASSIGNED: This paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated.
UNASSIGNED: Seventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects\' stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects\' serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up.
UNASSIGNED: (1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p < 0.05), while the Simpson index was significantly lower (p < 0.05) following the treatment. (2) Metabolites of the intestinal flora: the observation group had significantly higher levels of acetic acid, butyric acid, and valeric acid (p < 0.05), as well as lower levels of propionic acid (p < 0.05) following the treatment. (3) Nutritional status (the primary endpoint): following the treatment, the above serum nutritional indices were significantly higher in both groups (p < 0.05), while the indices of the observation group were significantly higher than those of the control group (p < 0.05).
UNASSIGNED: The rTMS method may improve the nutritional status of patients with PVS by regulating the structure of the intestinal flora and affecting the level of SCFAs through the microbiota-gut-brain axis. The possible mechanism involves how high-frequency rTMS can cause increased excitation in the frontal lobe of the right side of the brain, thus regulating the 5-hydroxytryptamine and norepinephrine levels.