Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Methodological considerations of priming repetitive transcranial magnetic stimulation protocols in clinical populations

INTRODUCTION Repetitive transcranial magnetic stimulation(rTMS)is a neuroplasticity-enhancing technique that modifies brain responsiveness to various therapeutic modalities in clinical psychiatric and neurological applications. Furthermore,its effect can be attributed to long-term potentiation(LTP)or longterm depression(LTD)-like neuroplasticity.However,responsiveness to rTMS is largely variable in healthy and pathological brains and is mediated by complex biological mechanisms.Metaplasticity refers to a higher-order plasticity mechanism in which the direction and magnitude of synaptic plasticity are modified by prior neuronal activity and is believed to be a significant factor leading to the response variability of rTMs.

Comparisons of transcranial alternating current stimulation and repetitive transcranial magnetic stimulation treatment therapy for insomnia:a pilot study

To the editor:Insomnia disorder has a serious and widespread detrimental effect on humans with comorbidity with other mental or physical health problems.In recent years,noninvasive brain stimulation(NIBS)techniques,especially transcranial magnetic stimulation(TMS)and transcranial electrical stimulation,have been increasingly used for the treatment of brain diseases,including insomnia disorder.

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.

Transcranial direct current stimulation efficacy in trigeminal neuralgia

Trigeminal neuralgia is a severe,disabling pain and its deafferentation remains a challenge for health providers.Transcranial direct current stimulation is a non-invasive stimulation technique which finds new utility in managing pain.There-fore,the introduction of alternative,non-invasive,safe,and effective methods should be considered in treating patients with trigeminal neuralgia unresponsive to conventional treatment.

Impact of transcranial electrical stimulation on serum neurotrophic factors and language function in patients with speech disorders

BACKGROUND Speech disorders have a substantial impact on communication abilities and quality of life.Traditional treatments such as speech and psychological therapies frequently demonstrate limited effectiveness and patient compliance.Transcranial electrical stimulation(TES)has emerged as a promising non-invasive treatment to improve neurological functions.However,its effectiveness in enhancing language functions and serum neurofactor levels in individuals with speech disorders requires further investigation.AIM To investigate the impact of TES in conjunction with standard therapies on serum neurotrophic factor levels and language function in patients with speech disorders.METHODS In a controlled study spanning from March 2019 to November 2021,81 patients with speech disorders were divided into a control group(n=40)receiving standard speech stimulation and psychological intervention,and an observation group(n=41)receiving additional TES.The study assessed serum levels of ciliary neurotrophic factor(CNTF),glial cell-derived neurotrophic factor(GDNF),brainderived neurotrophic factor(BDNF),and nerve growth factor(NGF),as well as evaluations of motor function,language function,and development quotient scores.RESULTS After 3 wk of intervention,the observation group exhibited significantly higher serum levels of CNTF,GDNF,BDNF,and NGF compared to the control group.Moreover,improvements were noted in motor function,cognitive function,language skills,physical abilities,and overall development quotient scores.It is worth mentioning that the observation group also displayed superior perfor CONCLUSION This retrospective study concluded that TES combined with traditional speech and psychotherapy can effectively increase the levels of neurokines in the blood and enhance language function in patients with speech disorders.These results provide a promising avenue for integrating TES into standard treatment methods for speech disorders.

Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient:A case report

BACKGROUND Supernumerary phantom limb(SPL)sensation is the experience of additional limbs,either single or a pair of limbs.Unique to traumatic spinal cord injuries,we report effect of transcranial direct current stimulation(tDCS)on SPL pain in a patient with cervical cord injury.CASE SUMMARY The subject was a 57-year-old man who was diagnosed with complete spinal cord injury(C6/C5,motor level;C5/C5,sensory level;AIS-A)approximately three months ago.After a period of 2 wk,we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 mA.Following that treatment,the patient experienced a decrease of SPL pain intensity and frequency,which lasted for 1 week after the end of treatment.CONCLUSION Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

“Flow” Transcranial Direct Current Stimulation (tDCS) for Depression Treatment in a Primary Healthcare General Practice—An Open-Label Cohort Study Measuring Montgomery-Åsberg Depression Rating Scale (MADRS-S) Outcomes

Background: Flow FL-100 is a transcranial direct current stimulation (tDCS) device self-administered by a patient at home in combination with a software application delivered wellbeing behaviour therapy training. tDCS has evidence of effectiveness in treating symptoms of depression. Purpose/Aim: This post marketing study evaluated the effect of Flow on depression for primary care general practice patients with depression symptoms. Methods: Open-label patient cohort design with no control group. Inclusion criteria were aged 18 years or over and reporting depression symptoms. Participants self-administered five 30 minute tDCS sessions per week for the first three weeks, and then 3 sessions per week following this. Three, six and ten week assessment with participant self-report measure: Montgomery- Åsberg Depression Rating Scale (MADRS-S). Results: MADRS-S remission rates were between 29% - 30% at three weeks, 33% - 34% at six-weeks and 50% at 10-weeks treatment. There was a significant improvement in MADRS-S with large effect sizes at all time points. Conclusions: Flow tDCS can be delivered through a primary healthcare general practice service and patients will choose to use. Flow tDCS provides an effective depression treatment in addition and as an alternative to antidepressants and psychotherapy. tDCS has evidence as an effective depression treatment, and the widespread availability of tDCS in primary care general practice should be considered.

Transcranial Direct Current Stimulation: Effects on Motor and Non-Motor Symptoms of Parkinson’s Disease

Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson’s disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2 mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

Positive Effect of Transcranial Direct Current Stimulation on Visual Verbal Working Memory in Patients with Attention-Deficit/Hyperactivity Disorder

Background: Working memory is an executive function that plays an important role in many aspects of daily life, and its impairment in patients with attention-deficit/hyperactivity disorder (ADHD) affects quality of life. The dorsolateral prefrontal cortex (DLPFC) has been a good target site for transcranial direct current stimulation (tDCS) due to its intense involvement in working memory. In our 2018 study, tDCS improved visual-verbal working memory in healthy subjects. Objective: This study examines the effects of tDCS on ADHD patients, particularly on verbal working memory. Methods: We conducted an experiment involving verbal working memory of two modalities, visual and auditory, and a sustained attention task that could affect working memory in 9 ADHD patients. Active or sham tDCS was applied to the left DLPFC in a single-blind crossover design. Results: tDCS significantly improved the accuracy of visual-verbal working memory. In contrast, tDCS did not affect auditory-verbal working memory and sustained attention. Conclusion: tDCS to the left DLPFC improved visual-verbal working memory in ADHD patients, with important implications for potential ADHD treatments.

Transcranial direct current stimulation as early augmentation in adolescent obsessive compulsive disorder:A pilot proof-of-concept randomized control trial

BACKGROUND Transcranial direct current stimulation(tDCS)is proven to be safe in treating various neurological conditions in children and adolescents.It is also an effective method in the treatment of OCD in adults.AIM To assess the safety and efficacy of tDCS as an add-on therapy in drug-naive adolescents with OCD.METHODS We studied drug-naïve adolescents with OCD,using a Children’s Yale-Brown obsessive-compulsive scale(CY-BOCS)scale to assess their condition.Both active and sham groups were given fluoxetine,and we applied cathode and anode over the supplementary motor area and deltoid for 20 min in 10 sessions.Reassessment occurred at 2,6,and 12 wk using CY-BOCS.RESULTS Eighteen adolescents completed the study(10-active,8-sham group).CY-BOCS scores from baseline to 12 wk reduced significantly in both groups but change at baseline to 2 wk was significant in the active group only.The mean change at 2 wk was more in the active group(11.8±7.77 vs 5.25±2.22,P=0.056).Adverse effects between the groups were comparable.CONCLUSION tDCS is safe and well tolerated for the treatment of OCD in adolescents.However,there is a need for further studies with a larger sample population to confirm the effectiveness of tDCS as early augmentation in OCD in this population.

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.

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.

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.

Acute effect of twice-daily 15 mA transcranial alternating current stimulation on treatment-resistant depression: a case series study

Totheeditor:Major depressive disorder(MDD)is a principal cause of disability worldwide and is often associated with high morbidity and mortality rates.Although there are several therapies available for the treatment of depression,about one-third of patients with MMD will not respond to two or more antidepressant drugs with different mechanisms;the patients are then referred to as having treatment-resistant depression(TRD).Patients with TRD have a poorer quality of life,greater economic burden and increased suicidal behaviours.Therefore,new antidepressant treatments that are effective,safe,long-lasting and tolerable are needed.Ketamine infusion,intranasal esketamine and transcranial magnetic stimulation(TMS)have been used to treat early stage TRD.’A recent review suggests that electroconvulsive therapy(ECT)may be superior to ketamine for reducing depression severity in the acute treatment of TRD.

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.

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.