Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

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.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression

Background Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation(DBS).The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression(TRD).Aims The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD.Methods Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis(BNST)-nucleus accumbens(NAc)DBS.White matter(WM)properties were extracted and compared between the response/non-response and remission/non-remission groups.Structural connectome was constructed and analysed using graph theory.Distances of the volume of activated tissue(VAT)to the main modulating tracts were also estimated to evaluate the correlations.Results Differences in fibre bundle properties of tracts,including superior thalamic radiation and reticulospinal tract,were observed between the remission and nonremission groups.Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups(p=0.010,t=3.07).The normalised clustering coefficient(γ)and the small-world property(σ)in graph analysis correlated with the symptom improvement after the correction of age.Conclusions Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions,as well as the distance of the VAT to the modulating tracts,may influence the clinical outcome of BNST-NAc DBS.These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

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.

“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.

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.

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.

Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical thrombectomy.In chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

Analysis of the Effect of Transcutaneous Electrical Stimulation of Acupoints Combined with Rehabilitation Training in The Treatment of Upper Limb Dysfunction After Stroke

Objective:To analyze the effect of combining transcutaneous electrical acupoint stimulation(TEAS)with rehabilitation training in patients with upper limb dysfunction after stroke(ULDAS).Methods:A total of 130 ULDAS patients who were hospitalized and rehabilitated in Wuxi Xinwu District Rehabilitation Hospital from May 2021 to May 2023 were selected and randomly divided into Group A(65 cases,rehabilitation training)and Group B(65 cases,rehabilitation training+TEAS).The effects of the two groups were compared.Results:After treatment,the upper limb functional indexes of Group B were better than those of Group A(P<0.05).The rate of muscle tone grades 0-4 in Group B was higher than those of Group A(P<0.05).Conclusion:The function of upper limbs and muscle strength of ULDAS patients improved by combining TEAS with rehabilitation training.

Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s disease.The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years.As a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive deficits.This article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound therapy.Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms.We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque deposition.We believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

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.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders

Alcohol use disorder （AUD）, mild traumatic brain injury （mTBI）, and posttraumatic stress disorder （PTSD） commonly co-occur （AUD ＋ mTBI ＋ PTSD）. These conditions have overlapping symptoms which are, in part, reflective of overlapping neuropathology. These conditions become problematic because their co-occurrence can exacerbate symptoms. Therefore, treatments must be developed that are inclusive to all three conditions. Repetitive transcranial magnetic stimulation （rTMS） is non-invasive and may be an ideal treatment for co-occurring AUD ＋ mTBI ＋ PTSD. There is accumulating evidence on rTMS as a treatment for people with AUD, mTBI, and PTSD each alone. However, there are no published studies to date on rTMS as a treatment for co-occurring AUD ＋ mTBI ＋ PTSD. This review article advances the knowledge base for rTMS as a treatment for AUD ＋ mTBI ＋ PTSD. This review provides background information about these co-occurring conditions as well as rTMS. The existing literature on rTMS as a treatment for people with AUD, TBI, and PTSD each alone is reviewed. Finally, neurobiological findings in support of a theoretical model are discussed to inform TMS as a treatment for co-occurring AUD ＋ mTBI ＋ PTSD. The peer-reviewed literature was identified by targeted literature searches using PubMed and supplemented by cross-referencing the bibliographies of relevant review articles. The existing evidence on rTMS as a treatment for these conditions in isolation, coupled with the overlapping neuropathology and symptomology of these conditions, suggests that rTMS may be well suited for the treatment of these conditions together.

Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous system,PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels.Therefore,the basic mechanisms of PNI have not been comprehensively understood.Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI,as well as to alleviate neuropathic pain,the specific mechanisms of successful PNI treatment are unclear.We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation.After PNI,activity in the central nervous system(spinal cord)is altered,which can limit regeneration of the damaged nerve.For example,cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission.The injured site of the peripheral nerve is also an important factor affecting post-PNI repair.After PNI,the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site.A slow speed of axon regeneration leads to low nerve regeneration.Therefore,it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site.From the perspective of target organs,long-term denervation can cause atrophy of the corresponding skeletal muscle,which leads to abnormal sensory perception and hyperalgesia,and finally,the loss of target organ function.The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping,addressing the excessive excitability of the dorsal root ganglion,alleviating neuropathic pain,improving neurological function,and accelerating nerve regeneration.Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function.Findings from the included studies confirm that after PNI,a series of physiological and pathological changes occur in the spinal cord,injury site,and target organs,leading to dysfunction.Electrical stimulation may address the pathophysiological changes mentioned above,thus promoting nerve regeneration and ameliorating dysfunction.

Deep Brain Stimulation──A new treatment for tinnitus

Intractable tinnitus can lead to serious consequences. Study evidence indicates that the central nervous system is involved in generation and maintenance of chronic tinnitus and that tinnitus and other neurologic symptoms such as chronic pain may share similar mechanisms. Brain ablation and stimulation are used to treat chronic pain with success. Recent studies showed that ablation and stimulation in non-auditory areas resulted in tinnitus improvement. Deep brain stimulation (DBS) may be an alternative treatment for intractable tinnitus and deserves further study.

Efficacy of repetitive transcranial magnetic stimulation in treatmentresistant depression:the evidence thus far

Depression is a common mental disorder, which attributes to significant morbidity, disability and burden of care. A significant number of patients with depression still remain symptomatic after adequate trials of antidepressant treatment as well as psychotherapy, which is often referred to as treatment-resistant depression. Neuromodulation techniques—like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, may be useful augmenting techniques in depression, mostly recommended for treatment-resistant cases. Robust evidence exists regarding the efficacy of electroconvulsive therapy in the management of treatment-resistant depression;however, other techniques are understudied. TMS has been increasingly studied in various psychiatric disorders including depression. It has been approved by the US Food and Drug Administration for use in major depressive disorder. Over the past two decades, TMS has been studied in diverse groups of the population with depression using several research designs. This article gives an overview of the efficacy of repetitive TMS in treatment-resistant depression with the recent evidence.

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.

Non-invasive electrical brain stimulation:from acute to late-stage treatment of central nervous system damage

Non-invasive brain current stimulation（NIBS） is a promising and versatile tool for inducing neuroplasticity,protection and functional rehabilitation of damaged neuronal systems.It is technically simple,requires no surgery,and has significant beneficial effects.However,there are various technical approaches for NIBS which influence neuronal networks in significantly different ways.Transcranial direct current stimulation（t DCS）,alternating current stimulation（ACS） and repetitive transcranial magnetic stimulation（r TMS） all have been applied to modulate brain activity in animal experiments under normal and pathological conditions.Also clinical trials have shown that t DCS,r TMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective mechanisms.The diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task,such as current type and strength,timing,distribution of current densities and electrode position.In this review,we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration,motor rehabilitation and cognitive enhancement.