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.

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.

Alzheimer's disease with depressive symptoms: Clinical effect of intermittent theta burst stimulation repetitive transcranial magnetic stimulation

BACKGROUND Alzheimer's disease(AD),characterized by the ongoing deterioration of neural function,often presents alongside depressive features and greatly affects the quality of life of individuals living with the condition.Although several treatment methods exist,their efficacy is limited.In recent years,repetitive transcranial magnetic stimulation(rTMS)utilizing the theta burst stimulation(TBS)mode,specifically the intermittent TBS(iTBS),has demonstrated promising therapeutic potential in the management of neuropsychiatric disorders.AIM To examine the therapeutic efficacy of iTBS mode of rTMS for treating depressive symptoms in patients with AD.METHODS This retrospective study enrolled 105 individuals diagnosed with AD with depressive symptoms at Huzhou Third Municipal Hospital,affiliated with Huzhou University,between January 2020 and December 2023.Participants received standard pharmacological interventions and were categorized into control(n=53)and observation(n=52)groups based on treatment protocols.The observation group received iTBS mode of rTMS,while the control group received pseudo-stimulation.A comparative analysis evaluated psychological well-being,adverse events,and therapeutic at initiation of hospitalization(T0)and 15 days post-treatment(T1).RESULTS At T1,both groups exhibited a marked reduction in self-rating depression scale and Hamilton depression scale scores compared to T0.Furthermore,the observa-tion group showed a more pronounced decrease than the control group.By T1,the Mini-mental state examination scores for both groups had increased markedly from their initial T0 assessments.Importantly,the increase was particularly more substantial in the observation group than in the control group.Fourteen patients in the control group had ineffective treatment effects,while five patients in the observation group experienced the same.Additionally,the observation group experienced a substantially reduced incidence of ineffective treatment as compared to the control group(both P<0.05);there were no recorded serious adverse events in either group.CONCLUSION The iTBS model of rTMS effectively treated AD with depression,improving depressive symptoms and cognitive function in patients without serious adverse reactions,warranting clinical consideration.

Comparing pharmacotherapy and transcranial magnetic stimulation for the treatment of anxiety and depression after aortic dissection surgery

BACKGROUND Aortic coarctation is a potentially fatal condition that is primarily treated surgically.Despite successful procedures,patients frequently experience postoperative anxiety and depression,which can hinder recovery and worsen outcomes.Pharmacological interventions,such as 5-hydroxytryptamine(5-HT)and norepinephrine reuptake inhibitors,are commonly prescribed;however,their efficacy alone or in combination with non-invasive brain stimulation techniques,such as repetitive transcranial magnetic stimulation(TMS),remains unclear.AIM To assess the effect of medications and TMS on post-aortic surgery anxiety and depression.METHODS We analyzed the outcomes of 151 patients with anxiety and depression who were hospitalized for aortic dissection between January 2020 and September 2022.Using the random number table method,75 and 76 patients were allocated to the normal control and study groups,respectively.All the patients were treated using routine procedures.The control group was administered anti-anxiety and antidepression drugs,whereas the study group was treated with TMS in addition to these medications.The patients in both groups showed improvement after two courses of treatment.The Hamilton Anxiety Scale(HAMA)and the Hamilton Depression Scale(HAMD)were used to assess anxiety and depression,respectively.The serum levels of brain-derived neurotrophic factor(BDNF)and 5-HT were determined using enzyme-linked immunosorbent assay.The Pittsburgh Sleep Quality Index(PSQI)was used to estimate sleep quality,and the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)was used to assess cognitive function.RESULTS The HAMD and HAMA scores reduced in 2 groups,with the study group achieving a lower level than control(P<0.05).In the control group,43 patients recovered,17 showed improvement,and 15 were deemed invalid.In the study group,52 recovered,20 improved,and four were invalid.The efficacy rate in study group was 94.74%compared to 80.00%in control(P<0.05).The BDNF and 5-HT levels increased in both groups,with higher levels observed in the experimental group(P<0.05).Moreover,the PSQI scores decreased in 2 groups,but were lower in the intervention group than control(P<0.05).The scores of the RBANS items increased,with the study group scoring higher than control(P<0.05).CONCLUSION Combining anti-anxiety and anti-depressive drugs with repetitive TMS after aortic surgery may enhance mood and treatment outcomes,offering a promising clinical approach.

Repetitive transcranial magnetic stimulation enhanced by neuronavigation in the treatment of depressive disorder and schizophrenia

This editorial assesses the advancements in neuronavigation enhanced repetitive transcranial magnetic stimulation for depressive disorder and schizophrenia treatment.Conventional repetitive transcranial magnetic stimulation faces challenges due to the intricacies of brain anatomy and patient variability.Neuronavigation offers innovative solutions by integrating neuroimaging with three-dimensional localization to pinpoint brain regions and refine therapeutic targeting.This systematic review of recent literature underscores the enhanced efficacy of neuronavigation in improving treatment outcomes for these disorders.This editorial highlights the pivotal role of neuronavigation in advancing psychiatric care.

Research hotspots and trends in transcranial magnetic stimulation for cognitive impairment:A bibliometric analysis from 2014 to 2023

BACKGROUND Cognitive impairment,which manifests as a limited deterioration of specific functions associated with a particular disease,can lead to a general deterioration of the patient’s standard of living.Transcranial magnetic stimulation,a noninvasive neuromodulation technique,is frequently employed to treat cognitive impairment in neuropsychiatric disorders.AIM To analyzed the state of international research on neuromodulation methods for treating cognitive impairment between 2014 and 2023,with the aim of exploring the state of research worldwide and the most recent developments in this particular area.METHODS Articles and reviews pertaining to neuromodulation methods for cognitive impairment were examined using the web of science database between January 2014 and December 2023.Publications,nations,organizations,writers,journals,citations,and keywords data from the identified studies were systematically analyzed using the CiteSpace 6.3.R1 software.RESULTS A total of 2371 documents with 11750 authors and 9461 institutions,with some cooccurrences,were retrieved.The quantity of yearly publications is showing an increasing trend.The United States and China have emerged as important contributors.Among the institutes,Harvard University had the highest number of publications,while Rossi S an author who is frequently cited.Initially,the primary keywords included human motor cortex,placebo-controlled trials,and serotonin reuptake inhibitors.However,the emphasis gradually moved to substance use disorders,supplementary motor areas,neural mechanisms,and exercise.CONCLUSION The use of neuromodulation techniques to treat cognitive impairment has drawn interest from academics all around the world.This study revealed hotspots and new trends in the research of transcranial magnetic stimulation as a cognitive impairment rehabilitation treatment.These findings are hold significant potential to guide further research and thus promote transcranial magnetic stimulation as a treatment method for cognitive impairment.

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.

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.

Increased activation of the caudate nucleus and parahippocampal gyrus in Parkinson's disease patients with dysphagia after repetitive transcranial magnetic stimulation:a case-control study

Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the corresponding brain regions in this patient group.In this casecontrol study,we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy,Capital Medical University.The patients received high-frequency r TMS of the motor cortex once per day for 10 successive days.Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls.The results revealed that before treatment,PD patients with dysphagia showed greater activation in the precentral gyrus,supplementary motor area,and cerebellum compared with healthy controls,and this enhanced activation was weakened after treatment.Furthermore,before treatment,PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus,caudate nucleus,and left thalamus compared with healthy controls,and this activation increased after treatment.In addition,PD patients with dysphagia reported improved subjective swallowing sensations after r TMS.These findings suggest that swallowing function in PD patients with dysphagia improved after r TMS of the motor cortex.This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus.The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University(approval No.2018 bkky017)on March 6,2018 and was registered with Chinese Clinical Trial Registry(registration No.Chi CTR 1800017207)on July 18,2018.

EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION ON MOTOR CORTICAL EXCITABILITY AND NEUROFUNCTION AFTER CEREBRAL ISCHEMIA-REPERFUSION INJURY IN RATS

Objective To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitabi- lity and neurofunction after cerebral ischemia-reperfusion injury. Methods After determined awake resting motor threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion injury, then rTMS were applied to rTMS group (n = 10) at different time, while control group (n = 10) received no stimulation. A week later, MT and MEPs were evaluated again, as well as neurological deficits and infarct volume. The effects of rTMS and MCAO reperfusion injury on these parameters were analyzed. Results After MCAO reperfusion, both MT level and neurological deficit scores increased, distinct focal infarction formed, and latency of MEP elongated. Compared with the control group, the increased extent of MT and neurological scores of rats receiving rTMS were significantly lower (P < 0.05), as well as the infarct volumes reduced significantly(P < 0.05). But MEP was not affected by rTMS obviously. There was a positive linear correlation between postinjury MT and infarct volume (r = 0.64, P < 0.05). Conclusion rTMS may facilitate neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could provide prognostic information after MCAO reperfusion injury.

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.

Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment:a double-blind randomized sham-controlled trial

Individuals with amnestic mild cognitive impairment(aMCI)have a high risk of developing Alzheimer’s disease.Although repetitive transcranial magnetic stimulation(rTMS)is considered a potentially effective treatment for cognitive impairment in patients with aMCI,the neuroimaging mechanisms are poorly understood.Therefore,we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University,China.Twenty-four patients with aMCI were randomly assigned to receive true rTMS(treatment group,n=12,6 men and 6 women;age 65.08±4.89 years)or sham stimulation(sham group,n=12,5 men and 7 women;age 64.67±4.77 years).rTMS parameters included a stimulation frequency of 10 Hz,stimulation duration of 2 seconds,stimulation interval of 8 seconds,20 repetitions at 80%of the motor threshold,and 400 pulses per session.rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks.Our results showed that compared with baseline,Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation(ALFF)was significantly increased at the end of treatment and 1 month after treatment.Compared with the sham group,the ALFF values in the right inferior frontal gyrus,triangular part of the inferior frontal gyrus,right precuneus,left angular gyrus,and right supramarginal gyrus were significantly increased,and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group.These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas.This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University,China(approval No.BYL20190901)on September 3,2019 and registered in the Chinese Clinical Trials Registry(registration No.ChiCTR1900028180)on December 14,2019.

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.

Effect of Transcranial Magnetic Stimulation on the Expression of c-Fos and Brain-derived Neurotrophic Factor of the Cerebral Cortex in Rats with Cerebral Infarct

The effect of transcranial magnetic stimulation （TMS） on the neurological functional recovery and expression of c-Fos and brain-derived neurotrophic factor （BDNF） of the cerebral cortex in rats with cerebral infarction was investigated. Cerebral infarction models were established by using left middle cerebral artery occlusion （MCAO） and were randomly divided into a model group （n=40） and a TMS group （n=40）. TMS treatment （2 times per day, 30 pulses per time） with a frequency of 0.5 Hz and magnetic field intensity of 1.33 Tesla was carried out in TMS group after MCAO. Modified neurological severity score （NSS） were recorded before and 1, 7, 14, 21, and 28 day（s） after MCAO. The expression of c-Fos and BDNF was immunohistochemically detected 1, 7, 14, 21, and 28 day（s） after infarction respectively. Our results showed that a significant recovery of NSS （P〈0.05） was found in animals treated by TMS on day 7, 14, 21, and 28 as compared with the animals in the model group. The positive expression of c-Fos and BDNF was detected in the cortex surrounding the infarction areas, while the expression of c-Fos and BDNF increased significantly in TMS treatment group in comparison with those in model group 7, 14, 21, and 28 days （P〈0.05） and 7 14, 21 days （P〈0.01） after infarction, respectively. It is concluded that TMS has therapeutic effect on cerebral infarction and this may have something to do with TMS＇s ability to promote the expression of c-Fos and BDNF of the cerebral cortex in rats with cerebral infarction.