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.

The Effect of Low Frequency Repetitive Transcranial Magnetic Stimulation Combined with Range of Motion Exercise on Paretic Hand Function in Female Patients after Stroke

Repetitive transcranial magnetic stimulation (rTMS) has recently been demonstrated to improve motor function after stroke. However, no study has yet tested the synergetic effects of physical exercise on rTMS in clinical settings. We investigated the effect of a 6-session course of low frequency rTMS on contralesional primary motor cortex combined with range-of motion (ROM) exercise on paretic hand function in female stroke patients. This was a single-blind study of the effects of rTMS with or without ROM exercise in female hemiplegic patients after stroke. All patients underwent rTMS on the contralesional primary motor cortex for 15 minutes and ROM exercise on the paretic hand. The cortical excitability determined by the amplitude and latency of the motor evoked potential (MEP) was measured in both first dorsal interosseous (FDI) muscles. We also evaluated arm function using Box and Block, arm reach, 9-hole pegboard, power grip, and pinch grip force tests. The rTMS-induced MEP amplitude of the paretic side significantly increased whereas the non-paretic side showed a decrease through every session. However, the MEP latency significantly increased on the non-paretic hand at post-rTMS with exercise, but a tendency of decrement on paretic hand at same application. Motor function showed improvement in the 9-hole pegboard and arm reach tests at post-rTMS with exercise on the paretic side compared with the non-paretic side. A significant correlation was especially noted between motor function and MEP on the paretic side of stroke patients. Low frequency rTMS with ROM exercise improved hand function after stroke. This may, in part, result in additional rehabilitation in stroke patients.

Effect of ultra-low frequency repetitive transcranial magnetic stimulation on dysphagia in elderly patients with acute cerebral infarction and quality of life

Objective:To investigate the clinical effect of ultra-low frequency repetitive transcranial magnetic stimulation on dysphagia in elderly patients with acute cerebral infarction and its impact on quality of life.Methods:60 elderly patients with dysphagia caused by acute cerebral infarction were randomly divided into rTMS group and control group,30 cases in each group.Both groups received routine drug therapy and swallowing function training.rTMS group was additionally treated by ultra-low frequency(10mHZ)repetitive transcranial magnetic stimulation for 14 days.The changes of NIHSS score andADL score and NSE serum level and Wa Tian drinking water experiment and Fujishima Ichiro dysphagia scale score and SWAL-QOL score and SF-36 score were observed between the two groups before and after treatment.The clinical effect was evaluated by Wa Tian drinking water experiment.Results:After treatment,The clinical effective rate in rTMS group was significantly higher compared with that in the control group(P<0.05),NIHSS score and serum NSE level were significantly lower compared with the control group(P<0.05),ADL score and Fujishima Ichiro dysphagia score and SWAL-QOL score and SF-36 scores were significantly higher compared with the control group(P<0.05).After treatment,SF-36 total score(or SWAL-QOL Score)was negatively correlated with NSE serum level and NIHSS score,which was positively correlated with ADL score and Fujishima Ichiro dysphagia scale score score.Conclusion:Ultra-low frequency rTMS therapy can reduce NSE level,effectively improve dysphagia in elderly patients with acute cerebral infarction and significantly improve the elderly patients'life quality.

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.

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.

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.

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.

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.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation on KCC2 Expression in Rats with Spasticity Following Spinal Cord Injury

The effect of high-frequency repetitive transcranial magnetic stimulation（r TMS） on potassium-chloride cotransporter-2（KCC2） protein expression following spinal cord injury（SCI） and the action mechanism were investigated. SCI models were established in SD rats. Five groups were set up randomly： normal control group, SCI 7-day（7 D） model group, SCI 14-day（14 D） model group, SCI-7 DrTMS group and SCI-14 DrTMS group（n=5 each）. The rats in SCI rTMS groups were treated with 10 Hz rTMS from 8 th day and 15 th day after SCI respectively, once every day, 5 days every week, a total of 4 weeks. After the model establishment, motor recovery and spasticity alleviation were evaluated with BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of variations of KCC2 protein using Western blotting and polymerase chain reaction（PCR） technique. The results showed that the BBS scores after treatment were significantly higher in SCI-7 DrTMS group than in SCI-14 DrTMS group（P〈0.05）. As compared with normal control groups, The KCC2 protein in SCI model groups was down-regulated after SCI, and the decrease was much more significant in SCI-14 D model group than in SCI-7 D group（P〈0.05）. As compared with SCI model groups, KCC2 protein in rTMS groups was up-regulated after the treatment（P〈0.05）. The up-regulation of KCC2 protein content and expression was more obvious in SCI-7 DrTMS group than in SCI-14 DrTMS group（P〈0.05）. It was concluded that 10 Hz rTMS can alleviate spasticity in rats with SCI, which might be attributed to the up-regulation of KCC2 protein. It was also suggested that the high-frequency rTMS treatment after SCI at early stage might achieve more satisfactory curative effectiveness.

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.

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.

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.

Low-frequency repetitive transcranial magnetic simulation prevents chronic epileptic seizure

Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcranial magnetic simulation on changes in several nonlinear dynamic electroenceph-alographic parameters in rats with chronic epilepsy and explored the mechanism underlying repeti-tive transcranial magnetic simulation-induced antiepileptic effects. An epilepsy model was estab-lished using lithium-pilocarpine intraperitoneal injection into adult Sprague-Dawley rats, which were then treated with repetitive transcranial magnetic simulation for 7 consecutive days. Nonlinear elec-electroencephalographic parameters were obtained from the rats at 7, 14, and 28 days post-stimulation. Results showed significantly lower mean correlation-dimension and Kolmogo-rov-entropy values for stimulated rats than for non-stimulated rats. At 28 days, the complexity and point-wise correlation dimensional values were lower in stimulated rats. Low-frequency repetitive transcranial magnetic simulation has suppressive effects on electrical activity in epileptic rats, thus explaining its effectiveness in treating epilepsy.

Delayed improvements in visual memory task performance among chronic schizophrenia patients after high-frequency repetitive transcranial magnetic stimulation

BACKGROUND Cognitive impairments are core characteristics of schizophrenia,but are largely resistant to current treatments.Several recent studies have shown that highfrequency repetitive transcranial magnetic stimulation(rTMS)of the left dorsolateral prefrontal cortex(DLPFC)can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients.However,results are inconsistent across studies.AIM To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODS Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC(n=25)or sham stimulation(n=22)on weekdays for four consecutive weeks.Patients performed the pattern recognition memory(PRM)task from the Cambridge Neuropsychological Test Automated Battery at baseline,at the end of rTMS treatment(week 4),and 4 wk after rTMS treatment(week 8).Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms(SANS)and the Positive and Negative Syndrome Scale(PANSS).RESULTS There were no significant differences in PRM performance metrics,SANS total score,SANS subscores,PANSS total score,and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period,but PRM performance metrics(percent correct and number correct)and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group(all P<0.05).Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment.Moreover,the improvement in visual memory was correlated with the reduction in negative symptoms at week 8.In contrast,there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8(all P>0.05).CONCLUSION High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia,but these effects are delayed,potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.

Different frequencies of repetitive transcranial magnetic stimulation combined with local injection of botulinum toxin type A for post-stroke lower limb spasticity:study protocol for a prospective,single-center,non-randomized,controlled clinical trial

No definite consensus has currently been reached regarding the safety and efficacy of low-or high-frequency repetitive transcranial magnetic stimulation in the treatment of post-stroke muscle spasticity.The latest research indicates that when combined with local injections of botulinum toxin type A,it is more effective on post-stroke muscle spasticity than local injections of botulinum toxin type A alone.We designed a prospective,single-center,non-randomized,controlled clinical trial to investigate the safety and effica cy of different frequencies of repetitive transcranial magnetic stimulation combined with local injections of botulinum toxin type A in treating post-stroke lower limb muscle spasticity to determine an optimal therapeutic regimen.This trial will enroll 150 patients with post-stroke muscle spasticity admitted to the Department of Rehabilitation Medicine at the First Affiliated Hos pital of China Medical Unive rsity.All enrolled patients will undergo ro utine rehabilitation training and will be divided into five groups in-30 per group) according to the particular area of cerebral infa rction and treatment methods.G roup A:Patients with massive cerebral infarction will be given local injections of botulinum toxin type A and low-frequency(1 Hz)repetitive transcranial magnetic stimulation on the contralate ral side;G roup B:Patients with non-massive cerebral infarction will be given local injections of botulinum toxin type A and high-frequency(10-20 Hz) re petitive transcranial magnetic stimulation on the affected side;G roup C:Patients with massive/non-massive cerebral infarction will be given local injections of botulinum toxin type A;G roup D:Patients with massive cerebral infarction will be given low-frequency(1 Hz) repetitive transcranial magnetic stimulation on the contralate ral side;and G roup E:Patients with non-massive cerebral infa rction will be given high-frequency(10-20 Hz) repetitive transcranial magnetic stimulation on the affected side.The primary outcome measure of this trial is a modified Ashwo rth scale score from 1 day before treatment to 12 months after treatment.Secondary outcome measures include Fugl-M eyer Assessment of Lower Extremity,Visual Analogue Scale,modified Barthel index,and Berg Balance Scale scores for the same time as specified for primary outcome measures.The safety indicator is the incidence of adverse events at 3-12 months after treatment.We hope to draw a definite conclusion on whether there are diffe rences in the safety and efficacy of low-or high-frequency repetitive transcranial magnetic stimulation combined with botulinum toxin type A injections in the treatment of patients with post-stroke lower limb spasticity under strict grouping and standardized operation,thereby screening out the optimal therapeutic regimen.The study protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of China Medical University(approval No.[2021] 2021-333-3) on August 19,2021.The trial was registe red with the Chinese Clinical Trial Registry(Registration No.ChiCTR2100052180) on October 21,2021.The protocol version is 1.1.

Optimising repetitive transcranial magnetic stimulation for neural circuit repair following traumatic brain injury

While it is well-known that neuronal activity promotes plasticity and connectivity, the success of activity-based neural rehabilitation programs remains extremely limited in human clinical experience because they cannot adequately control neuronal excitability and activity within the injured brain in order to induce repair. However, it is possible to non-invasively modulate brain plasticity using brain stimu- lation techniques such as repetitive transcranial （rTMS） and transcranial direct current stimulation （tDCS） techniques, which show promise for repairing injured neural circuits （Henrich-Noack et al., 2013; Lefaucher et al., 2014）. Yet we are far from having full control of these techniques to repair the brain following neurotrauma and need more fundamen- tal research （Ellaway et al., 2014; Lefaucher et al., 2014）. In this perspective we discuss the mechanisms by which rTMS may facilitate neurorehabilitation and propose experimental techniques with which magnetic stimulation may be investi- gated in order to optimise its treatment potential.

Effect of repetitive transcranial magnetic stimulation combined with swallowing training on the nutritional status and neurological function of patients with dysphigin after stroke

Objective: To study the effect of repetitive transcranial magnetic stimulation combined with swallowing training on the nutritional status and neurological function of patients with dysphigin after stroke. Methods: Patients with dysphagia after stroke who received rehabilitation in Nanjing Brain Hospital between June 2014 and September 2016 were selected and randomly divided into magnetic stimulation + training group and training group who received repetitive transcranial magnetic stimulation combined with swallowing training and swallowing training alone respectively. The nutritional status indexes, nerve injury indexes and neurotrophy indexes in serum were determined before treatment and 28 d after treatment. Results: 28 d after treatment, serum ALB, Hb, PAB, TRF, IGF-1, BDNF, NGF and VEGF contents of both groups of patients were higher than those before treatment while VILIP-1, NSE, Fibulin-5, NPY and Nogo-A contents were lower than those before treatment, and serum ALB, Hb, PAB, TRF, IGF-1, BDNF, NGF and VEGF contents of magnetic stimulation+ training group were higher than those of training group while VILIP-1, NSE, Fibulin-5, NPY and Nogo-A contents were lower than those of training group. Conclusion: Repetitive transcranial magnetic stimulation combined with swallowing training for dysphigin after stroke can improve the nutritional status and improve the neurological function.

High frequency heart rate variability evoked by repetitive transcranial magnetic stimulation over the medial prefrontal cortex: A preliminary investigation on brain processing of acute stressor-evoked cardiovascular reactivity

Introduction: Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for brain stimulation. Repetitive TMS (rTMS) over the medial Prefrontal Cortex (mPFC), Broadman Area 10 (BA10) may stimulate transynaptically perigenual Anterior Cingulate Cortex (pACC, BA 33), insula, amigdala, hypothalamus and connected branches of the Autonomic Nervous System (ANS) involved in stressorevoked cardiovascular reactivity. Stressors are associated with an increase in sympathetic cardiac control, a decrease in parasympathetic control, or both, and, consequently, an increase in systolic/stroke volume, total vascular impedance/resistance and heart rate, a decrease of baroreflex sensitivity, i.e., an increase in blood pressure/arterial tension. Objectives and Aims: The present work aims, using TMS and accordingly to Gianaros modeling, based on functional neuroimaging studies and previous neuroanatomical data from animal models, to probe the connectivity of brain systems involved in stressor-evoked cardiovascular reactivity and to explore TMS potential as a tool for detection and stratification of individual differences concerning this reactivity and hemorreological risk factors correlated with the development of Coronary Heart Disease (CHD). Methods: Both subjects, a 52 years old male and a 40 years old female with previous increased Low Frequency (LF)/High Frequency (HF) Heart Rate Variability (HRV) ratios (respectively, 4.209/3.028) without decompensated cardiorespiratory symptoms, gave informed consent, and ethico-legal issues have been observed. Electroencephalographic (EEG) monitoring has been performed for safety purposes. Immediately after administration, over the mPFC, of 15 pulses of rTMS, during 60 second, with an inductive electrical current, at the stimulating coil, of 85.9 Ampère per μsecond and 66 Ampère per μsecond, respectively, for male and female subjects (a “figure-of-eight” coil and magnetic stimulator MagLite, Dantec/Medtronic, have been used), HRV spectrum analysis (cStress software) has been performed (during 5 minutes, in supine position). Results: In both subjects, LF power, HF power and LF/HF ratio results, before and after rTMS administration, pointed towards sympathetic attenuation and parasympathetic augmentation (respectively, in male/female subject: decreased LF power—65.1 nu/69.3 nu, before rTMS;56.1 nu/41.6 nu, after rTMS;increased HF power—15.5 nu/22.9 nu, before rTMS;30.9 nu/45.5 nu, after rTMS). Conclusions: In this preliminary investigation, the existence of a link between “mind” and heart’s function has been put in evidence, through a reversible “virtual” lesion, of brain systems involved in cardiovascular control, caused by TMS. Repetitive TMS over mPFC decreased brain function involved in stressorevoked cardiovascular reactivity, suggesting the importance of TMS in the management of stress-related cardiovascular disorders.

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.