Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
BACKGROUND Depression has become a global public health problem.In recent years,transcranial magnetic stimulation(TMS)has gained considerable attention as a noninvasive treatment for depression.AIM To investigate the ...BACKGROUND Depression has become a global public health problem.In recent years,transcranial magnetic stimulation(TMS)has gained considerable attention as a noninvasive treatment for depression.AIM To investigate the research hotspots and trends in the field of TMS-based depression treatment from a bibliometric perspective.METHODS Using the Web of Science Core Collection,articles published between 2003 and 2022 on TMS-based depression treatment were retrieved from the science citation index expanded.The publication trends and research hotspots were analyzed using VOSviewer,CiteSpace,and the bibliometric online analysis platform.Regression analysis was performed using Microsoft Excel 2021 to predict publication growth trends.RESULTS We identified a total of 702 articles on TMS-based depression treatment with a predominance of clinical studies.Analysis of collaborative networks showed that the United States,the University of Toronto,and Daskalakis ZJ were identified as the most impactful country,institution,and researcher,respectively.In keyword burst analysis,it was found that theta burst stimulation(TBS),functional connectivity,and frequency were the most recent research hotspots.CONCLUSION TMS provides a novel therapeutic option for patients with treatment-resistant depression.Neuroimaging technology enables more precise TMS treatment,while the novel TMS modality,TBS,enhances both therapeutic efficacy and patient experience in TMS-based depression treatment.The integration of neuroimaging techniques with TBS represents a promising research direction for advancing TMS-based depression treatment.This study presents systematic information and recommendations to guide future research on TMS-based depression treatment.展开更多
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 mitigati...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.展开更多
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 prog...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.展开更多
Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance to...Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.展开更多
Stroke remains a leading cause of long-term disability worldwide.There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery.Transc...Stroke remains a leading cause of long-term disability worldwide.There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery.Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke.However,previously published research has only investigated a narrow range of stimulation settings and indications.In this review,we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials.We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke,highlighting their indications,parameter settings,scope,and limitations.We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation,focusing on critical aspects such as stimulation settings,target groups,biomarkers,and integration with rehabilitation interventions.展开更多
Transcranial temporal interference stimulation(tTIS)is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures.This study explores the neural and behavioral effects ...Transcranial temporal interference stimulation(tTIS)is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures.This study explores the neural and behavioral effects of tTIS on the superior colliculus(SC),a region involved in eye movement control,in mice.Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation.In vivo experiments,including Ca^(2+)signal recordings and eye movement tracking,showed that tTIS effectively modulates SC neural activity and induces eye movements.A significant correlation was found between stimulation frequency and saccade frequency,suggesting direct tTIS-induced modulation of SC activity.These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements,highlighting its potential for neuroscientific research and therapeutic applications.展开更多
To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial mag...To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial magnetic stimulation(rTMS),one of the most commonly applied non-invasive neurostimulation techniques,has shown efficacy in treating neuropsychiatric disorders,such as depression.展开更多
BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder,with limited evidence for pharmacotherapy.Treatment typically involves medication,cognitive behavioral therapy,and behavioral interventions.Re...BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder,with limited evidence for pharmacotherapy.Treatment typically involves medication,cognitive behavioral therapy,and behavioral interventions.Recently,transcranial magnetic stimulation(TMS)has emerged as a potential treatment strategy.AIM To assess the role of TMS in treating trichotillomania.METHODS A systematic search using specific terms was done in PubMed and Scopus databases for articles published until May 17,2024,related to trichotillomania and TMS.The search included randomized controlled trials,open-label studies,case series,case reports,and retrospective chart reviews,following the Preferred Items for Systematic Reviews and Meta-Analysis guideline.RESULTS We identified 32 articles(6 in PubMed and 26 in Scopus).After removing duplicates and articles that did not meet the selection criteria,we conducted a final analysis of four articles.These included one retrospective study,two case series,and one case study,with a total of 22 patients diagnosed with trichotillomania enrolled across all four studies.The brain areas targeted were the supplementary motor area(SMA),pre-SMA,and left dorsolateral prefrontal cortex.The studies reported an improvement in the severity of symptoms of trichotillomania in the majority of patients with negligible side effects.Nevertheless,it is important to note that the existing studies are mostly of low to moderate quality.CONCLUSION Early evidence suggests repetitive TMS and accelerated continuous theta burst stimulation can help treat trichotillomania adjunctively to other treatments.展开更多
Background Pain sensitivity is critical for preventing non-suicidal self-injury(NSSI)behaviours;however,individuals engaging in such behaviours often exhibit decreased pain sensitivity,which may undermine this natural...Background Pain sensitivity is critical for preventing non-suicidal self-injury(NSSI)behaviours;however,individuals engaging in such behaviours often exhibit decreased pain sensitivity,which may undermine this natural safeguard.The dorsolateral prefrontal cortex(DLPFC)is a key region involved in pain regulation,and recent approaches using transcranial direct current stimulation(tDCS)to target the DLPFC have shown potential for modulating pain processing and restoring normal pain perception for individuals engaging in NSSI behaviours.Aims This study aimed to explore the immediate and short-term effects of a single session of tDCS on pain sensitivity in individuals with NSSI,as well as its secondary effects on mood and NSSI-related factors.Methods In this randomised,double-blind,parallel,sham-controlled clinical trial,participants with a history of NSSI were randomly assigned to receive either active or sham tDCS.The intervention consisted of a single 20 min tDCS session targeting the left DLPFC.The primary outcome was pain sensitivity,measured by the pressure pain threshold(PPT)and heat pain score(HPS).Secondary and additional outcomes included NSSI urges,NSSI resistance,self-efficacy in resisting NSSI,mood-related variables and exploratory cognitive-affective processes such as rumination,self-criticism and self-perceived pain sensitivity,assessed at baseline,immediately post-intervention,and at 24 hours,1 week and 2 weeks follow-ups.Results For the primary outcomes,no significant differences between groups were observed for pain sensitivity(PPT,padj=0.812;HPS,padj=0.608).However,an exploratory sensitivity analysis treating each trial as an individual observation revealed a significant effect on HPS(padj=0.036).For the secondary and additional outcomes,although there were initial improvements in joyful feelings and reductions in negative affect at 2 weeks post-intervention,these effects did not remain significant after multiple comparison corrections.Notably,reductions in rumination were statistically significant at both 1-week and 2-week follow-ups(1 week,p_(adj)=0.040;2 weeks,p_(adj)=0.042).There were no significant effects on NSSI urges,NSSI resistance,self-efficacy in resisting NSSI or self-criticism.Conclusions A single session of tDCS over the left DLPFC did not produce significant changes in pain sensitivity in individuals with NSSI.A sensitivity analysis indicated an effect on heat pain sensitivity,possibly reflecting changes in brain activity,warranting confirmation through neuroimaging.These findings suggest that tDCS warrants further investigation for its potential to influence pain-related cognitive-affective processes in individuals with NSSI.展开更多
BACKGROUND The prevalence of addiction makes it a significant public health issue.Recently,transcranial magnetic stimulation(TMS)has garnered significant attention as a promising treatment for addiction.AIM To analyze...BACKGROUND The prevalence of addiction makes it a significant public health issue.Recently,transcranial magnetic stimulation(TMS)has garnered significant attention as a promising treatment for addiction.AIM To analyze development trends and research hotspots in TMS-based addiction treatment using a bibliometric approach.METHODS Articles on TMS-based addiction treatment from 2001 to 2023 were sourced from the Science Citation Index Expanded in the Web of Science Core Collection.CiteSpace software,VOSviewer,the"bibliometrix"R software package,and the bibliometric online analysis platform were used to analyze the current publication trends and hotspots.RESULTS Total 190 articles on TMS-based addiction treatment were identified,with clinical studies being the most prevalent.The United States led in both publication volume and international collaborations.Medical University of South Carolina and Zangen A were the most productive institution and author,respectively.Neurobiology,alcohol use disorder,and repetitive TMS were the most recent research hotspots.CONCLUSION Future research should focus on the neurobiological mechanisms underlying TMS-based addiction treatment.This study offers comprehensive insights and recommendations for advancing research on TMS-based addiction treatment.展开更多
Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to t...Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.展开更多
Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,whic...Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,which is characterized by less adverse reaction and convenient operation.It has been widely used in the treatment of various diseases.This review introduces six major clinical applications of TEAS,named analgesia,regulation of gastrointestinal function,improvement of reproductive function,enhancement of cognitive function,promotion of limb function recovery and relief of fatigue.Besides,TEAS has been ap-plied to the treatment of other chronic diseases such as hypertension and diabetes,achieving satisfactory clinical effects.However,two crucial challenges are encountered in the development of TEAS.One is the lack of standardization in the selection of parameters such as waveform,frequency,intensity and stimula-tion duration.The other is the limitation on the flexibility in the acupoint selection.This review analyzes key issues that need to be addressed in the current clinical application of TEAS,such as the selection of parameters and acupoints,and this review provides a certain reference value for optimizing regimens of TEAS and promoting its development and application.展开更多
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 neur...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.展开更多
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...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).展开更多
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Adv...Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.展开更多
Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize...Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.展开更多
Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple o...Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.展开更多
Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despit...Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.展开更多
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金Supported by the National Natural Science Foundation of China,No.82270916,No.81800748 and No.82371478the Third Affiliated Hospital of Anhui Medical University Basic and Clinical Collaborative Research Enhancement Program Cultivation Special Funding Project,No.2022sfy009.
文摘BACKGROUND Depression has become a global public health problem.In recent years,transcranial magnetic stimulation(TMS)has gained considerable attention as a noninvasive treatment for depression.AIM To investigate the research hotspots and trends in the field of TMS-based depression treatment from a bibliometric perspective.METHODS Using the Web of Science Core Collection,articles published between 2003 and 2022 on TMS-based depression treatment were retrieved from the science citation index expanded.The publication trends and research hotspots were analyzed using VOSviewer,CiteSpace,and the bibliometric online analysis platform.Regression analysis was performed using Microsoft Excel 2021 to predict publication growth trends.RESULTS We identified a total of 702 articles on TMS-based depression treatment with a predominance of clinical studies.Analysis of collaborative networks showed that the United States,the University of Toronto,and Daskalakis ZJ were identified as the most impactful country,institution,and researcher,respectively.In keyword burst analysis,it was found that theta burst stimulation(TBS),functional connectivity,and frequency were the most recent research hotspots.CONCLUSION TMS provides a novel therapeutic option for patients with treatment-resistant depression.Neuroimaging technology enables more precise TMS treatment,while the novel TMS modality,TBS,enhances both therapeutic efficacy and patient experience in TMS-based depression treatment.The integration of neuroimaging techniques with TBS represents a promising research direction for advancing TMS-based depression treatment.This study presents systematic information and recommendations to guide future research on TMS-based depression treatment.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘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.
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘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.
基金supported by the Fundamental Research Funds for the Central Universities,Nos.G2021KY05107,G2021KY05101the National Natural Science Foundation of China,Nos.32071316,32211530049+1 种基金the Natural Science Foundation of Shaanxi Province,No.2022-JM482the Education and Teaching Reform Funds for the Central Universities,No.23GZ230102(all to LL and HH).
文摘Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.
基金an Association of British Neurologists Doctoral Research Fellowship co-funded by the Berkeley Foundation and the Stroke Associationsupported by a NIHR Academic Clinical Lectureship in Neurology CL-2020-04-004 NIHR+3 种基金supported by the NIHR Sheffield Biomedical Research Centre(BRC)NIHR Sheffield Clinical Research Facility(CRF)supported by NIHR EME Project Grant NIHR133169funded by Alzheimer’s Research UK Senior Research Fellowship(ARUK-SRF2017B-1)。
文摘Stroke remains a leading cause of long-term disability worldwide.There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery.Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke.However,previously published research has only investigated a narrow range of stimulation settings and indications.In this review,we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials.We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke,highlighting their indications,parameter settings,scope,and limitations.We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation,focusing on critical aspects such as stimulation settings,target groups,biomarkers,and integration with rehabilitation interventions.
基金supported by the National Natural Science Foundation of China(T2394533,32222036,82030038,and 62472206)the National Key Research and Development Program of China(2018YFA0701400)the Shenzhen Science and Technology Innovation Committee(2022410129,KJZD20230923115221044,and KCXFZ20201221173400001).
文摘Transcranial temporal interference stimulation(tTIS)is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures.This study explores the neural and behavioral effects of tTIS on the superior colliculus(SC),a region involved in eye movement control,in mice.Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation.In vivo experiments,including Ca^(2+)signal recordings and eye movement tracking,showed that tTIS effectively modulates SC neural activity and induces eye movements.A significant correlation was found between stimulation frequency and saccade frequency,suggesting direct tTIS-induced modulation of SC activity.These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements,highlighting its potential for neuroscientific research and therapeutic applications.
基金supported by grants from the National Natural Science Foundation of China(82125032,81930095,82204048 and 81761128035)the Science and Technology Commission of Shanghai Municipality(19410713500 and 2018SHZDZX01)+3 种基金the Foundation of Shanghai Municipal Commission of Health and Family Planning(GWV-10.1-XK07,2020CXJQ01 and 2018YJRC03)the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20211100)the Guangdong Key Project(2018B030335001).
文摘To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial magnetic stimulation(rTMS),one of the most commonly applied non-invasive neurostimulation techniques,has shown efficacy in treating neuropsychiatric disorders,such as depression.
文摘BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder,with limited evidence for pharmacotherapy.Treatment typically involves medication,cognitive behavioral therapy,and behavioral interventions.Recently,transcranial magnetic stimulation(TMS)has emerged as a potential treatment strategy.AIM To assess the role of TMS in treating trichotillomania.METHODS A systematic search using specific terms was done in PubMed and Scopus databases for articles published until May 17,2024,related to trichotillomania and TMS.The search included randomized controlled trials,open-label studies,case series,case reports,and retrospective chart reviews,following the Preferred Items for Systematic Reviews and Meta-Analysis guideline.RESULTS We identified 32 articles(6 in PubMed and 26 in Scopus).After removing duplicates and articles that did not meet the selection criteria,we conducted a final analysis of four articles.These included one retrospective study,two case series,and one case study,with a total of 22 patients diagnosed with trichotillomania enrolled across all four studies.The brain areas targeted were the supplementary motor area(SMA),pre-SMA,and left dorsolateral prefrontal cortex.The studies reported an improvement in the severity of symptoms of trichotillomania in the majority of patients with negligible side effects.Nevertheless,it is important to note that the existing studies are mostly of low to moderate quality.CONCLUSION Early evidence suggests repetitive TMS and accelerated continuous theta burst stimulation can help treat trichotillomania adjunctively to other treatments.
基金supported by National Natural Science Foundation of China(82471564)YT is supported by National Natural Science Foundation of China(32322035,32171078).
文摘Background Pain sensitivity is critical for preventing non-suicidal self-injury(NSSI)behaviours;however,individuals engaging in such behaviours often exhibit decreased pain sensitivity,which may undermine this natural safeguard.The dorsolateral prefrontal cortex(DLPFC)is a key region involved in pain regulation,and recent approaches using transcranial direct current stimulation(tDCS)to target the DLPFC have shown potential for modulating pain processing and restoring normal pain perception for individuals engaging in NSSI behaviours.Aims This study aimed to explore the immediate and short-term effects of a single session of tDCS on pain sensitivity in individuals with NSSI,as well as its secondary effects on mood and NSSI-related factors.Methods In this randomised,double-blind,parallel,sham-controlled clinical trial,participants with a history of NSSI were randomly assigned to receive either active or sham tDCS.The intervention consisted of a single 20 min tDCS session targeting the left DLPFC.The primary outcome was pain sensitivity,measured by the pressure pain threshold(PPT)and heat pain score(HPS).Secondary and additional outcomes included NSSI urges,NSSI resistance,self-efficacy in resisting NSSI,mood-related variables and exploratory cognitive-affective processes such as rumination,self-criticism and self-perceived pain sensitivity,assessed at baseline,immediately post-intervention,and at 24 hours,1 week and 2 weeks follow-ups.Results For the primary outcomes,no significant differences between groups were observed for pain sensitivity(PPT,padj=0.812;HPS,padj=0.608).However,an exploratory sensitivity analysis treating each trial as an individual observation revealed a significant effect on HPS(padj=0.036).For the secondary and additional outcomes,although there were initial improvements in joyful feelings and reductions in negative affect at 2 weeks post-intervention,these effects did not remain significant after multiple comparison corrections.Notably,reductions in rumination were statistically significant at both 1-week and 2-week follow-ups(1 week,p_(adj)=0.040;2 weeks,p_(adj)=0.042).There were no significant effects on NSSI urges,NSSI resistance,self-efficacy in resisting NSSI or self-criticism.Conclusions A single session of tDCS over the left DLPFC did not produce significant changes in pain sensitivity in individuals with NSSI.A sensitivity analysis indicated an effect on heat pain sensitivity,possibly reflecting changes in brain activity,warranting confirmation through neuroimaging.These findings suggest that tDCS warrants further investigation for its potential to influence pain-related cognitive-affective processes in individuals with NSSI.
基金Supported by National Natural Science Foundation of China,No.81973620Wenzhou Municipal Science and Technology Bureau,No.Y20220091.
文摘BACKGROUND The prevalence of addiction makes it a significant public health issue.Recently,transcranial magnetic stimulation(TMS)has garnered significant attention as a promising treatment for addiction.AIM To analyze development trends and research hotspots in TMS-based addiction treatment using a bibliometric approach.METHODS Articles on TMS-based addiction treatment from 2001 to 2023 were sourced from the Science Citation Index Expanded in the Web of Science Core Collection.CiteSpace software,VOSviewer,the"bibliometrix"R software package,and the bibliometric online analysis platform were used to analyze the current publication trends and hotspots.RESULTS Total 190 articles on TMS-based addiction treatment were identified,with clinical studies being the most prevalent.The United States led in both publication volume and international collaborations.Medical University of South Carolina and Zangen A were the most productive institution and author,respectively.Neurobiology,alcohol use disorder,and repetitive TMS were the most recent research hotspots.CONCLUSION Future research should focus on the neurobiological mechanisms underlying TMS-based addiction treatment.This study offers comprehensive insights and recommendations for advancing research on TMS-based addiction treatment.
基金the scope of the CICS-UBI projects UIDP/Multi/00709/2019,UIDB/Multi/00709/2019,UIDP/00709/2020,UIDB/00709/2020,financed by national funds through the Portuguese Foundation for Science and Technology/MCTESby funds to the PPBI-Portuguese Platform of Bio Imaging through the Project POCI-01-0145-FEDER-022122(to GB,MVP,NP)supported by a grant from the Portuguese Foundation for Science and Technology/MCTES(2021.07854.BD)(to IS)。
文摘Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.
基金Supported by Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special Program:20Y21902800Shanghai Municipal Health Commission Shanghai Three-Year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine Inheritance and Innovation:ZY(2021-2023)−0302)+1 种基金Shanghai Key Specialty(Acupuncture)Construction Project:shslczdzk04701Shanghai 2024"Science and Technology Innovation Action Plan"star cultivation(Sail special):24YF2740600.
文摘Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,which is characterized by less adverse reaction and convenient operation.It has been widely used in the treatment of various diseases.This review introduces six major clinical applications of TEAS,named analgesia,regulation of gastrointestinal function,improvement of reproductive function,enhancement of cognitive function,promotion of limb function recovery and relief of fatigue.Besides,TEAS has been ap-plied to the treatment of other chronic diseases such as hypertension and diabetes,achieving satisfactory clinical effects.However,two crucial challenges are encountered in the development of TEAS.One is the lack of standardization in the selection of parameters such as waveform,frequency,intensity and stimula-tion duration.The other is the limitation on the flexibility in the acupoint selection.This review analyzes key issues that need to be addressed in the current clinical application of TEAS,such as the selection of parameters and acupoints,and this review provides a certain reference value for optimizing regimens of TEAS and promoting its development and application.
基金supported by the Hefei Comprehensive National Science Center Hefei Brain Project(to KW)the National Natural Science Foundation of China,Nos.31970979(to KW),82101498(to XW)the STI2030-Major Projects,No.2021ZD0201800(to PH).
文摘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.
基金supported by on Association of British Neurologists Fellowship(Stroke Association/Berkeley Foundation)supported by the NIHR Sheffield Biomedical Research Centre。
文摘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).
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
基金supported by the National Natural Science Foundation of China(Nos.T2293730,T2293731,62121003,61960206012,61973292,62171434,61975206,and 61971400)the National Key Research and Development Program of China(Nos.2022YFC2402501 and 2022YFB3205602)+1 种基金the Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.GJJSTD20210004).
文摘Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.
基金supported by STI 2030-Major Projects,No.2021ZD0201603(to JL)the Joint Foundation Program of the Chinese Academy of Sciences,No.8091A170201(to JL)+1 种基金the National Natural Science Foundation of China,Nos.T2293730(to XC),T2293731(to XC),T2293734(to XC),62471291(to YW),62121003(to XC),61960206012(to XC),62333020(to XC),and 62171434(to XC)the National Key Research and Development Program of China,Nos.2022YFC2402501(to XC),2022YFB3205602(to XC).
文摘Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.
基金National Natural Science Foundation of China(31930103)National Center of Technology Innovation for Pigs(NCTIP-XD/B03)+2 种基金Ningbo Major Science and Technology Project(2021Z112)National Key R&D Program(2022YFD1300303)Beijing Innovation Consortium of Livestock Research System BAIC05-2024.
文摘Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.
基金supported by the Defitech Foundation(Morges,CH)to FCHthe Bertarelli Foundation-Catalyst program(Gstaad,CH)to FCH+2 种基金the Wyss Center for Bio and Neuroengineering the Lighthouse Partnership for AI-guided Neuromodulation to FCHthe Fonds de recherche du Quebec-Sante(FRQS#342969)to CEPthe Neuro X Postdoctoral Fellowship Program to CEP。
文摘Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.
