High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.

Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

Analyzing the Combination Effects of Repetitive Transcranial Magnetic Stimulation and Motor Control Training on Balance Function and Gait in Patients with Stroke-Induced Hemiplegia

Objective:To analyze the effects of repetitive transcranial magnetic stimulation combined with motor control training on the treatment of stroke-induced hemiplegia,specifically focusing on the impact on patients’balance function and gait.Methods:Fifty-two cases of hemiplegic stroke patients were randomly divided into two groups,26 in the control group and 26 in the observation group,using computer-generated random grouping.All participants underwent conventional treatment and rehabilitation training.In addition to these,the control group received repetitive transcranial magnetic pseudo-stimulation therapy+motor control training,while the observation group received repetitive transcranial magnetic stimulation therapy+motor control training.The balance function and gait parameters of both groups were compared before and after the interventions and assessed the satisfaction of the interventions in both groups.Results:Before the invention,there were no significant differences in balance function scores and each gait parameter between the two groups(P>0.05).However,after the intervention,the observation group showed higher balance function scores compared to the control group(P<0.05).The observation group also exhibited higher step speed and step frequency,longer step length,and a higher overall satisfaction level with the intervention compared to the control group(P<0.05).Conclusion:The combination of repetitive transcranial magnetic stimulation and motor control training in the treatment of stroke-induced hemiplegia has demonstrated positive effects.It not only improves the patient’s balance function and gait but also contributes to overall physical rehabilitation.

Analysis of the Effect of Limb Rehabilitation Therapy Combined with Transcranial Magnetic Stimulation Therapy on Muscle Activity in Patients with Upper Limb Dysfunction After Cerebral Infarction

Objective:To analyze the effect of limb rehabilitation therapy combined with transcranial magnetic stimulation therapy on muscle activity in patients with upper limb dysfunction after cerebral infarction(CI).Methods:320 patients with upper limb dysfunction after CI were selected,all of whom were treated in our hospital between June 2021 and June 2023.They were randomly grouped according to the lottery method into the control group(limb rehabilitation therapy,160 cases)and the intervention group(transcranial magnetic stimulation therapy+limb rehabilitation therapy,160 cases).The upper limb function scores,neuro-electrophysiological indicators,daily living ability scores,and quality of life scores of the two groups were compared.Results:Compared with the control group,upper limb function scores and daily living ability scores in the intervention group were higher after treatment,and the neuro-electrophysiological indicators of the intervention group were lower after treatment(P<0.05).Conclusion:Transcranial magnetic stimulation therapy combined with limb rehabilitation therapy has significant effects in patients with upper limb dysfunction after CI and is worthy of promotion and application.

Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins

Studies have shown that repetitive transcra nial magnetic stimulation(rTMS)can enhance synaptic plasticity and improve neurological dysfunction.Howeve r,the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood.In this study,we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS.To help determine the mechanism of action,we measured levels of seve ral impo rtant brain activity-related proteins and their mRNA.On the injured side of the brain,we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor,tropomyosin receptor kinase B,N-methyl-D-aspartic acid receptor 1,and phosphorylated cAMP response element binding protein,which are closely associated with the occurrence of long-term potentiation.rTMS also partially reve rsed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure.These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.

Mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation for ferroptosis after spinal cord injury

Spinal cord injury is characte rized by diffe rent aetiologies,complex pathogenesis,and diverse pathological changes.Current treatments are not ideal,and prognosis is generally poor.After spinal cord injury,neurons die due to various forms of cell death.Among them,fe rroptosis causes dysfunction after spinal cord injury,and no existing traditional treatments have been indicated to block its occurrence.Meanwhile,emerging therapies using mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation therapy are promising for reve rsing spinal co rd neuronal ferroptosis after spinal cord injury.However,no definitive studies have demonstrated the effectiveness of these approaches.This review summarizes the existing research on the mechanisms of ferroptosis;fe rroptosis after spinal cord injury;treatment of spinal cord injury with mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation;and treatment of ferroptosis using mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation.Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury.In addition,mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation can reve rse adverse outcomes of spinal cord injury and regulate ferroptosis-related fa ctors.Thus,it can be inferred that mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation have the potential to inhibit fe rroptosis after spinal cord injury.This review serves as a reference for future research to confirm these conclusions.

Past,present,and future of deep transcranial magnetic stimulation:A review in psychiatric and neurological disorders

Deep transcranial magnetic stimulation(DTMS)is a new non-invasive neuromodulation technique based on repetitive transcranial magnetic stimulation technology.The new H-coil has significant advantages in the treatment and mechanism research of psychiatric and neurological disorders.This is due to its deep stimulation site and wide range of action.This paper reviews the clinical progress of DTMS in psychiatric and neurological disorders such as Parkinson’s disease,Alzheimer’s disease,post-stroke motor dysfunction,aphasia,and other neurological disorders,as well as anxiety,depression,and schizophrenia.

Motor cortex transcranial magnetic stimulation to reduce intractable postherpetic neuralgia with poor response to other threapies:Report of two cases

BACKGROUND Postherpetic neuralgia(PHN)is a typical neuropathic pain condition that appears in the lesioned skin regions following the healing of shingles.The pain condition tends to persist,which is often accompanied by negative emotions(e.g.,anxiety and depression)and substantially reduces the quality of life.In addition to analgesia(e.g.,pregabalin and gabapentin),nerve radiofrequency technology is an effective treatment for intractable PHN.However,there is still a significant portion of patients who do not benefit from this treatment.As a non-invasive form of brain stimulation,repetitive transcranial magnetic stimulation(rTMS)targeting the motor cortex is able to reduce neuropathic pain with grade A evidence.CASE SUMMARY Here we report two cases in which motor cortex rTMS was used to treat intractable PHN that did not respond to initial drug and radiofrequency therapies.Moreover,we specifically investigated rTMS efficacy at 3 mo following treatment.CONCLUSION Motor cortex rTMS can treat intractable PHN that did not respond to initial drug and radiofrequency therapies.

Poststroke rehabilitation using repetitive transcranial magnetic stimulation during pregnancy:A case report

BACKGROUND Repetitive transcranial magnetic stimulation(rTMS)is a form of magnetic stimulation therapy used to treat depression,migraine,and motor function impairment in patients with stroke.As there is little research on the effects of rTMS in pregnant women,it is not widely used in these patients.This case report aimed to demonstrate the safety of rTMS in pregnant patients.CASE SUMMARY After much consideration,we applied rTMS to treat recent stroke and hemiplegia in a 34-year-old pregnant woman.The patient received 45 sessions of lowfrequency treatment over the course of 10 wk.We closely monitored the mother and fetus for potential side effects;the results showed significant improvement in the patient's motor function,with no harmful effects on the mother or fetus during pregnancy or after delivery.The patient’s fine motor and walking functions improved after treatment.This case is the first instance of a stroke patient treated with rTMS during pregnancy.CONCLUSION This case demonstrates that rTMS could be used to improve motor function recovery in stroke patients during pregnancy.

Effectiveness of antidepressant repetitive transcranial magnetic stimulation in a patient with refractory psychogenic dysphagia:A case report and review of literature

BACKGROUND Dysphagia is a common condition in older as well as young patients,and a variety of treatments have been reported depending on the cause.However,clinicians are challenged when the cause is unclear.This is the case with psychogenic dysphagia,which has typically been treated with supportive psychotherapy,medi-cation,swallowing exercise,and dysphagia rehabilitation therapy.Here,we aimed to relieve the symptoms of a patient with refractory psychogenic dysphagia,who was unresponsive to conventional swallowing therapy,with repetitive transcranial magnetic stimulation(rTMS).CASE SUMMARY A relatively calm-looking 35-year-old female patient presented with a 2-year history of dysphagia.She showed little improvement with conventional swallowing treatments over the past 2 years.She was relatively compliant with inhospital dysphagia therapy,but uncooperative with home exercise and medication.In particular,since she was resistant to drug treatment,we had to take a different approach than the treatment she had been receiving for the past 2 years.After much deliberation,we decided to initiate antidepressant rTMS treatment with her consent(IRB No.2023-05-021).Antidepressant rTMS treatment was performed twice weekly for a total of 20 sessions over 10 wk.The results showed improvement in subjective symptoms and video fluoroscopic swallowing study findings.To the best of our knowledge,this is the first report of symptomatic improvement using antidepressant rTMS protocol for refractory psychogenic dysphagia.CONCLUSION This case demonstrates that rTMS with antidepressant protocol can be used to improve swallowing in patients with refractory psychogenic dysphagia.

Clinical study of different modes of repetitive transcranial magnetic stimulation in the treatment of post‑stroke executive dysfunction

Objective:To investigate the clinical efficacy of intermittent theta burst stimulation(iTBS)and high frequency repetitive transcranial magnetic stimulation(rTMS)on post‑stroke executive impairment(PSEI).Methods:Ninety patients with PSEI who were hospitalized in the rehabilitation department of Xuzhou Central Hospital and Xuzhou Rehabilitation Hospital from April 2021 to June 2022 were selected and divided into iTBS group,high‑frequency group and control group.All three groups of patients received routine rehabilitation training,given rTMS treatment with iTBS,10 Hz and shame stimulation for 4 weeks.Before and after treatment,all the patients were evaluated with the Montreal cognitive assessment(MoCA),the frontal assessment battery(FAB),troop color‑word test(SCWT),shape trails test(STT),digit span test(DST)and event related potential P300.Results:After treatment,MoCA,FAB,SCWT,STT,DST scores,P300 latency and amplitude were significantly better in the three groups than before treatment(P<0.05).MoCA,FAB,SCWT,STT‑B,DST scores,P300 latency and amplitude in the iTBS group and high‑frequency group were better than in the control group,with significant differences(P<0.05).The difference between iTBS group and high‑frequency group was not statistically significant(P>0.05).Conclusion:iTBS can improve PSEI,and the efficacy is comparable to 10Hz rTMS.iTBS takes less time with better efficiency,and it is worth popularizing and applying in clinic.

Repetitive transcranial magnetic stimulation combined with olanzapine and amisulpride for treatment-refractory schizophrenia

BACKGROUND Treatment-refractory schizophrenia(TRS),accounting for approximately 30%of all schizophrenia cases,has poor treatment response and prognosis despite treatment with antipsychotic drugs.AIM To analyze the therapeutic effectiveness of repetitive transcranial magnetic stimulation(rTMS)combined with olanzapine(OLZ)and amisulpride(AMI)for TRS and its influence on the patient’s cognitive function.METHODS This study enrolled 114 TRS patients who received treatment at the First Affiliated Hospital of Zhengzhou University between July 2019 and July 2022.In addition to the basic OLZ+AMI therapy,54 cases of the control group(Con group)received modified electroconvulsive therapy,while 60 cases of the research group(Res group)received rTMS.Data on therapeutic effectiveness,safety(incidence of drowsiness,headache,nausea,vomiting,or memory impairment),Positive and Negative Symptom Scale,Montreal Cognitive Assessment Scale,and Schizophrenia Quality of Life Scale were collected from both cohorts for comparative analyses.RESULTS The Res group elicited a higher overall response rate and better safety profile when compared with the Con group.Additionally,a significant reduction was observed in the post-treatment Positive and Negative Symptom Scale and Schizophrenia Quality of Life Scale scores of the Res group,presenting lower scores than those of the Con group.Furthermore,a significant increase in the Montreal Cognitive Assessment Scale score was reported in the Res group,with higher scores than those of the Con group.CONCLUSION The treatment of TRS with rTMS and OLZ+AMI is effective and safe.Moreover,it can alleviate the patients’mental symptoms,improve their cognitive function and quality of life,and has a high clinical application value.

Transcranial magnetic stimulation in animal models of neurodegeneration

Brain stimulation techniques offer powerful means of modulating the physiology of specific neural structures. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation(TMS) and transcranial direct current stimulation, have emerged as therapeutic tools for neurology and neuroscience. However, the possible repercussions of these techniques remain unclear, and there are few reports on the incisive recovery mechanisms through brain stimulation. Although several studies have recommended the use of non-invasive brain stimulation in clinical neuroscience, with a special emphasis on TMS, the suggested mechanisms of action have not been confirmed directly at the neural level. Insights into the neural mechanisms of non-invasive brain stimulation would unveil the strategies necessary to enhance the safety and efficacy of this progressive approach. Therefore, animal studies investigating the mechanisms of TMSinduced recovery at the neural level are crucial for the elaboration of non-invasive brain stimulation. Translational research done using animal models has several advantages and is able to investigate knowledge gaps by directly targeting neuronal levels. In this review, we have discussed the role of TMS in different animal models, the impact of animal studies on various disease states, and the findings regarding brain function of animal models after TMS in pharmacology research.

Repetitive transcranial magnetic stimulation of language function in patients with refractory epilepsy A preliminary functional magnetic resonance imaging study

To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of language dysfunction, were recruited. Over 1 month, 1-Hz rTMS treatment was performed every 3 days. A battery of language production and functional MRI were evaluated in the patients using a standard verb generation task both before and 1 month after rTMS treatment. Significant and lasting improvement in verb production was observed following rTMS treatment. Functional MRI results revealed that the left frontal lobes of two patients were more activated than they had been prior to therapy, and activation was primarily concentrated in the language-related areas. Results demonstrated that low frequency rTMS has potential to improve language function in patients with refractory epilepsy.

Low frequency repetitive transcranial magnetic stimulation improves motor dysfunction after cerebral infarction

Low frequency （≤ 1 Hz） repetitive transcranial magnetic stimulation （rTMS） can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores （National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment） improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency （1 Hz） rTMS for 14 days can help improve motor function after cerebral infarction.

Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex （M1）. The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke:a systematic review and network meta-analysis

Transcranial magnetic stimulation,a type of noninvasive brain stimulation,has become an ancillary therapy for motor function rehabilitation.Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS)on motor function in stroke patients.There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke.The MEDLINE,Embase,Cochrane Library,ISI Science Citation Index,Physiotherapy Evidence Database,China National Knowledge Infrastructure Library,and ClinicalTrials.gov databases were searched.Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke,published from inception to November 28,2019,were included.Standard pairwise meta-analysis was conducted using R version 3.6.1 with the“meta”package.Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions.Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation.Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency rTMS or sham stimulation.These findings suggest that rTMS can improve motor function in patients with stroke,and that low-frequency rTMS mainly affects motor function,whereas high-frequency rTMS increases the amplitudes of motor evoked potentials.More highquality randomized controlled trials are needed to validate this conclusion.The work was registered in PROSPERO(registration No.CRD42020147055)on April 28,2020.

Effect of Acupuncture Cooperated with Low-frequency Repetitive Transcranial Magnetic Stimulation on Chronic Insomnia： A Randomized Clinical Trial

The effect of acupuncture cooperated with low-frequency repetitive transcranial magnetic stimulation （rTMS） on chronic insomnia was explored. Seventy-eight patients with chronic insomnia were randomly allocated into two groups： treatment group and control group. In the treatment group, the patients received acupuncture combined with rTMS treatment, and those in the control group were given acupuncture cooperated with sham rTMS treatment, 3 days per week for 4 weeks. Before and after treatment, the primary outcomes including the scores on Insomnia Severity Index （ISI） and Pittsburgh Sleep Quality Index （PSQI） and the secondary outcomes including total sleep time （TST）, sleep onset latency （SOL）, wake after sleep onset （WASO）, sleep efficiency （SE%） recorded by sleeping diary and actigraphy were observed in both groups. Seventy-five participants finished the study （38 in treatment group and 37 in control group respectively）. After treatment, the scores in the two groups were improved significantly, more significantly in the treatment group than in the control group. It can be inferred that acupuncture cooperated with rTMS can effectively improve sleep quality, enhance the quality of life of patients and has less side effects.

Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders A meta-analysis

OBJECTIVE： This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hallucination of patients with schizophrenia spectrum disorders. DATA SOURCES： Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Controlled Trials databases from January 1985 to May 2012. Key words were ＂transcranial magnetic stimulation＂, ＂TMS＂, ＂repetitive tran- scranial magnetic stimulation＂, and ＂hallucination＂. STUDY SELECTION： Selected studies were randomized controlled trials assessing therapeutic ef- ficacy of repetitive transcranial magnetic stimulation for hallucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hallucination in schizophrenia spectrum disorders. Control groups received sham stimulation. MAIN OUTCOME MEASURES： The primary outcome was total scores of Auditory Hallucinations Rating Scale, Auditory Hallucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hallucination item, and Hallucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. RESULTS： Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. All data were completely effective, involving 398 patients. Overall mean weighted effect size for repeti- tive transcranial magnetic stimulation versus sham stimulation was statistically significant （MD = -0.42, 95%C/： -0.64 to -0.20, P = 0.000 2）. Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation （OR = 2.94, 95%C/： 1.39 to 6.24, P =0.005）. No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for positive or negative symptoms. Compared with sham stimulation, active repeti- tive transcranial magnetic stimulation had equivocal outcome in cognitive function and commonly caused headache and facial muscle twitching. CONCLUSION： Repetitive transcranial magnetic stimulation is a safe and effective treatment for auditory hallucination in schizophrenia spectrum disorders,

Electro-acupuncture Combined with Transcranial Magnetic Stimulation Improves Learning and Memory Function of Rats with Cerebral Infarction by Inhibiting Neuron Cell Apoptosis

This study examined the effect of electro-acupuncture (EA) combined with transcranial magnetic stimulation (TMS) therapy at different time windows on learning and memory ability of rats with cerebral infarction and the underlying mechanism.Two hundred SD rats were randomly divided into four groups:normal group,sham-operated group,model group and EA+TMS group,and each group was then divided into five sub-groups in terms of the different time to start treatment post operation:6,12,24,48 and 72 h.Cerebral infarction models were established in the model and the EA+TMS groups by left middle cerebral artery occlusion/reperfusion (MCAO/R).After treatment for 14 d,the Morris water maze test was applied to examine the spatial learning and memory abilities of rats.In infarcted area,the expression of caspase-3 was immunohistochemically detected,and real-time fluorescent quantitative PCR was used to measure the expression of Bcl-2 mRNA.The results showed that in EA+TMS group compared with model group at the same treatment time windows,the escape latency was substantially shortened,the expression of caspase-3 was considerably decreased and the expression level of Bcl-2 mRNA significantly increased (P<0.05).In the EA+TMS sub-groups,the escape latency was shortest,the expression level of caspase-3 lowest,and the expression level of Bcl-2 mRNA highest at the treatment time window of 24 h.It was concluded that EA combined with TMS can promote neurological function of rats with cerebral infarction by increasing the expression level of Bcl-2 mRNA and decreasing the expression of caspase-3.The best time window is 24 h after perfusion treatment to ischemia.