Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical imp...Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.展开更多
There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nuc...There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.展开更多
Background and Objective Since its initial report by James Parkinson in 1817,Parkinson’s disease(PD)has remained a central subject of research and clinical advancement.The disease is estimated to affect approximately...Background and Objective Since its initial report by James Parkinson in 1817,Parkinson’s disease(PD)has remained a central subject of research and clinical advancement.The disease is estimated to affect approximately 1%of adults aged 60 and above.Deep brain stimulation,emerging as an alternative therapy for end-stage cases,has offered a lifeline to numerous patients.This review aimed to analyze publications pertaining to the impact of deep brain stimulation on the motor pathway in patients with PD over the last decade.Methods Data were obtained from the Web of Science Core Collection through the library of Huazhong University of Science and Technology(China).The search strategy encompassed the following keywords:“deep brain stimulation”,“Parkinson’s disease”,“motor pathway”,and“human”,from January 1,2012,to December 1,2022.Additionally,this review visualized the findings using the Citespace software.Results The results indicated that the United States,the United Kingdom,Germany,and China were the primary contributors to this research field.University College London,Capital Medical University,and Maastricht University were the top 3 research institutions in the research area.Tom Foltynie ranked first with 6 publications,and the journals of Brain and Brain Stimulation published the greatest number of relevant articles.The prevailing research focal points in this domain,as determined by keywords“burst analysis”,“encompassed neuronal activity”,“nucleus”,“hyper direct pathway”,etc.Conclusion This study has provided a new perspective through bibliometric analysis of the deep brain stimulation therapy for treating patients with PD,which can shed light on future research to advance our comprehension of this particular field of study.展开更多
Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic ...Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.展开更多
We conducted a systematic review of studies using non-invasive brain stimulation(NIBS: repetitive transcranial magnetic stimulation(r TMS) and transcranial direct current stimulation(t DCS)) as a research and clinical...We conducted a systematic review of studies using non-invasive brain stimulation(NIBS: repetitive transcranial magnetic stimulation(r TMS) and transcranial direct current stimulation(t DCS)) as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury(SCI) under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI.展开更多
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 symp...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.展开更多
Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of...Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of Parkinson’s disease(PD).In previous studies,the development of parkinsonian network dynamics modeling has made great progress.Modeling mainly focuses on the cortex-thalamus-basal ganglia(CTBG)circuit and its sub-circuits,which helps to explore the dynamic behavior of the parkinsonian network,such as synchronization.Deep brain stimulation(DBS)is an effective strategy for the treatment of PD.At present,many studies are based on the side effects of the DBS.However,the translation from modeling results to clinical disease mitigation therapy still faces huge challenges.Here,we introduce the progress of DBS improvement.Its specific purpose is to develop novel DBS treatment methods,optimize the treatment effect of DBS for each patient,and focus on the study in closed-loop DBS.Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.展开更多
Deep brain stimulation of the bilateral subthalamic nucleus(STN)is a therapeutic option for patients with Parkinson’s disease(PD)in whom medical therapies have been ineffective.This retrospective cohort study analyze...Deep brain stimulation of the bilateral subthalamic nucleus(STN)is a therapeutic option for patients with Parkinson’s disease(PD)in whom medical therapies have been ineffective.This retrospective cohort study analyzed the motor function of 27 patients with advanced PD,from the First Affiliated Hospital of Guangzhou Medical University,China,who received deep brain stimulation of the bilateral subthalamic nucleus and evaluated its therapeutic effects.The 10-year follow-up data of patients was analyzed in Qingyuan People’s Hospital,Sixth Affiliated Hospital of Guangzhou Medical University,China.The follow-up data were divided into two categories based on patients during levodopa treatment(on-medication)and without levodopa treatment(off-medication).Compared with baseline,the motor function of onmedication PD patients improved after deep brain stimulation of the bilateral subthalamic nucleus.Even 2 years later,the motor function of off-medication PD patients had improved.On-medication PD patients exhibited better therapeutic effects over the 5 years than offmedication PD patients.On-medication patients’akinesia,speech,postural stability,gait,and cognitive function worsened only after 5 years.These results suggest that the motor function of patients with advanced PD benefitted from treatment with deep brain stimulation of the bilateral subthalamic nucleus over a period up to 5 years.The overall therapeutic effects were more pronounced when levodopa treatment was combined with deep brain stimulation of the bilateral subthalamic nucleus.This study was approved by Institutional Review Board of Qingyuan People’s Hospital,The Sixth Affiliated Hospital of Guangzhou Medical University,China(approval No.QPH-IRB-A0140)on January 11,2018.展开更多
BACKGROUND:Subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) has achieved good effects,but to date the mechanism of STN DBS remains poorly understood. STN DBS may increase dopamine ...BACKGROUND:Subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) has achieved good effects,but to date the mechanism of STN DBS remains poorly understood. STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE:To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography (SPECT) and position emission tomography (PET). DESIGN,TIME AND SETTING:A controlled animal study was performed at the Neurosurgery Laboratory,Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. METHODS:Hemiparkinsonism was induced in adult Rhesus Macaque monkeys,which exhibit similar characteristics of PD in humans,through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1,2,3,6-tetrahydropyrindine. Following model establishment,stimulation electrodes were implanted in the right STN,and chronic high-frequency stimulation (60 μs pulse width,130 Hz frequency,and 1.5-2.0 V pressure) was performed. MAIN OUTCOME MEASURES:The changes in dopamine transporter (DAT),D2 receptor (D2R),and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS:SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation,and D2R specific binding in the right corpus striatum gradually decreased near levels on the left (non-electrode-implanted) side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity,increased activities,and stable gait under chronic high-frequency stimulation. CONCLUSION:STN DBS increased striatal DAT,decreased D2R,and enhanced glucose metabolism,suggesting that chronic,high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum,a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.展开更多
This paper provides an adaptive closed-loop strategy for suppressing the pathological oscillations of the basal ganglia based on a variable universe fuzzy algorithm.The pathological basal ganglia oscillations in the t...This paper provides an adaptive closed-loop strategy for suppressing the pathological oscillations of the basal ganglia based on a variable universe fuzzy algorithm.The pathological basal ganglia oscillations in the theta(4-9 Hz)and beta(12-35 Hz)frequency bands have been demonstrated to be associated with the tremor and rigidity/bradykinesia symptoms in Parkinson’s disease(PD).Although the clinical application of open-loop deep brain stimulation(DBS)is effective,the stimulation waveform with the fixed parameters cannot be self-adjusted as the disease progresses,and thus the stimulation effects go poor.To deal with this difficult problem,a variable universe fuzzy closed-loop strategy is proposed to modulate different PD states.We establish a cortico-basal ganglia-thalamocortical network model to simulate pathological oscillations and test the control effect.The results suggest that the proposed closed-loop control strategy can accommodate the variation of brain states and symptoms,which may become an alternative method to administrate the symptoms in PD.展开更多
BACKGROUND Forniceal deep brain stimulation(DBS)has been proposed as an alternative treatment for Alzheimer's disease(AD).Previous studies on mild to moderate AD patients demonstrated improvements in cognitive fun...BACKGROUND Forniceal deep brain stimulation(DBS)has been proposed as an alternative treatment for Alzheimer's disease(AD).Previous studies on mild to moderate AD patients demonstrated improvements in cognitive functions brought about by forniceal DBS.Here,we report our longitudinal findings in one severe AD patient for whom the activities of daily living(ADL)rather than cognitive function significantly improved after 3 mo of continuous stimulation.CASE SUMMARY In 2011,a 62-year-old Chinese male with no previous history of brain injury or other neuropsychological diseases and no family history of dementia developed early symptoms of memory decline and cognitive impairment.Five years later,the symptoms had increased to the extent that they affected his daily living.He lost the ability to work as a businessman and to take care of himself.The patient was given a clinical diagnosis of probable AD and was prescribed donepezil and subsequently memantine,but no improvement in symptoms was observed.The patient then received DBS surgery.After 3 mo of continuous stimulation,the patient's ADL score decreased from 65 points to 47 points,indicating the quality of the patient's daily living improved distinctly.Other scores remained unchanged,suggesting no significant improvement in cognitive function.A follow-up positron emission tomography scan demonstrated perceivable increased glucose metabolism in the classical AD-related brain regions.CONCLUSION Based on this case we hypothesize that forniceal DBS may improve ADL through elevating regional glucose metabolism in the brain.展开更多
Closed-loop deep brain stimulation(DBS):DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure hav...Closed-loop deep brain stimulation(DBS):DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure have been previously made.Several factors affect the DBS clinical outcomes such as lead position,programming technique,and surgical展开更多
BACKGROUND Twenty years after its first use in a patient with obsessive-compulsive disorder(OCD),the results confirm that deep brain stimulation(DBS)is a promising therapy for patients with severe and resistant forms ...BACKGROUND Twenty years after its first use in a patient with obsessive-compulsive disorder(OCD),the results confirm that deep brain stimulation(DBS)is a promising therapy for patients with severe and resistant forms of the disorder.Nevertheless,many unknowns remain,including the optimal anatomical targets,the best stimulation parameters,the long-term(LT)effects of the therapy,and the clinical or biological factors associated with response.This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response.AIM To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD.METHODS A comprehensive search was conducted in the PubMed,Cochrane,Scopus,and ClinicalTrials.gov databases from inception to December 31,2020,using the following strategy:“(Obsessive-compulsive disorder OR OCD)AND(deep brain stimulation OR DBS).”Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool.The inclusion criteria were as follows:a main diagnosis of OCD,DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale(Y-BOCS)as primary outcome.Data were analyzed with descriptive statistics.RESULTS Forty articles identified by the search strategy met the eligibility criteria.Applying a follow-up threshold of 36 mo,29 studies(with 230 patients)provided information on short-term(ST)response to DBS in,while 11(with 155 patients)reported results on LT response.Mean follow-up period was 18.5±8.0 mo for the ST studies and 63.7±20.7 mo for the LT studies.Overall,the percentage of reduction in Y-BOCS scores was similar in ST(47.4%)and LT responses(47.2%)to DBS,but more patients in the LT reports met the criteria for response(defined as a reduction in Y-BOCS scores>35%:ST,60.6%vs LT,70.7%).According to the results,the response in the first year predicts the extent to which an OCD patient will benefit from DBS,since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation.Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients;but it is still controversial whether this improvement persists,increases or decreases in the long term.Three different patterns of LT response emerged from the analysis:49.5% of patients had good and sustained response to DBS,26.6% were non responders,and 22.5% were partial responders,who might improve at some point but experience relapses during follow-up.A significant improvement in depressive symptoms and global functionality was observed in most studies,usually(although not always)in parallel with an improvement in obsessive symptoms.Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters;however,some severe adverse events including intracranial hemorrhages and infections were also described.Hypomania was the most frequently reported psychiatric side effect.The relationship between DBS and suicide risk is still controversial and requires further study.Finally,to date,no clear clinical or biological predictors of response can be established,probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed.CONCLUSION The present review confirms that DBS is a promising therapy for patients with severe resistant OCD,providing both ST and LT evidence of efficacy.展开更多
Parkinson’s disease (PD) is a neurodegenerative disease mainly caused by motor disorders, mostly occurring in middle-aged and elderly people. The incidence of PD has been increasing year by year, and up to now, PD is...Parkinson’s disease (PD) is a neurodegenerative disease mainly caused by motor disorders, mostly occurring in middle-aged and elderly people. The incidence of PD has been increasing year by year, and up to now, PD is still an incurable disease. However, more and more data show that early implementation of deep brain stimulation and early medical, psychological, social and other interventions can significantly improve the quality of life and prolong the survival time of patients with Parkinson’s disease (PD). Mental health guidance, cognitive behavioral intervention, psychogenic therapy and scientific nursing for PD patients may improve the functional recovery after Deep Brain Stimulation (DBS) for Parkinson’s disease. This paper discusses the nursing and psychological intervention methods of deep brain stimulation (DBS) implantation in patients with Parkinson’s disease (PD), aiming to scientifically discuss the clinical effect of nursing psychological intervention and improve the quality of life in patients with Parkinson’s disease. Basic nursing and psychological cognitive behavior intervention measures for PD patients can improve the daily activity ability of PD patients, improve the outcome of PD patients, and effectively improve the satisfaction of PD patients with nursing work, which has certain clinical promotion significance.展开更多
Deep brain stimulation offers an advanced means of treating Parkinson’s disease in a patient specific context. However, a considerable challenge is the process of ascertaining an optimal parameter configuration. Impe...Deep brain stimulation offers an advanced means of treating Parkinson’s disease in a patient specific context. However, a considerable challenge is the process of ascertaining an optimal parameter configuration. Imperative for the deep brain stimulation parameter optimization process is the quantification of response feedback. As a significant improvement to traditional ordinal scale techniques is the advent of wearable and wireless systems. Recently conformal wearable and wireless systems with a profile on the order of a bandage have been developed. Previous research endeavors have successfully differentiated between deep brain stimulation “On” and “Off” status through quantification using wearable and wireless inertial sensor systems. However, the opportunity exists to further evolve to an objectively quantified response to an assortment of parameter configurations, such as the variation of amplitude, for the deep brain stimulation system. Multiple deep brain stimulation amplitude settings are considered inclusive of “Off” status as a baseline, 1.0 mA, 2.5 mA, and 4.0 mA. The quantified response of this assortment of amplitude settings is acquired through a conformal wearable and wireless inertial sensor system and consolidated using Python software automation to a feature set amenable for machine learning. Five machine learning algorithms are evaluated: J48 decision tree, K-nearest neighbors, support vector machine, logistic regression, and random forest. The performance of these machine learning algorithms is established based on the classification accuracy to distinguish between the deep brain stimulation amplitude settings and the time to develop the machine learning model. The support vector machine achieves the greatest classification accuracy, which is the primary performance parameter, and <span style="font-family:Verdana;">K-nearest neighbors achieves considerable classification accuracy with minimal time to develop the machine learning model.</span>展开更多
Neurosurgical treatment for psychiatric disorders features a long and controversial history.This article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradu...Neurosurgical treatment for psychiatric disorders features a long and controversial history.This article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day,mainstream scientific deep brain stimulation(DBS).We focus on the rise,fall and possible re-emergence of psychosurgery as a therapeutic intervention today.We journey through historic indiscriminate use of prefrontal lobotomy,which evoked stern criticism from both public and professionals,through to the development of modern day DBS-performed for patients suffering from severe,treatment resistant symptoms of obsessive-compulsive disorder(OCD),epilepsy and movement disorders.We hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities,whilst simultaneously challenging any public/professional preconceptions of psychosurgery,which may indirectly be obstructing patient care.Additionally,we carried out a qualitative survey displayed in WordCloud Format,capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust,on“psychosurgery”,“prefrontal lobotomy”and“DBS”,which may well reflect wider public opinion.In summary,the article provides a brief,yet comprehensive overview of the controversial history of psychosurgery,present-day practice,and future trends of neurosurgery for psychiatric disorders.展开更多
Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals.The common neuromodulation techniques,including deep brain stimulation(DBS)and optogenetics,have excellent spatial...Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals.The common neuromodulation techniques,including deep brain stimulation(DBS)and optogenetics,have excellent spatial resolution and depth penetration but require implementation of electrodes or optical fibers.Therefore,it is important to develop methods for noninvasive modulation of telomere length.Herein,we reported on a new method for decelerating telomere shortening using noninvasive ultrasound deep brain stimulation(UDBS).Firstly,we found that UDBS could activate the telomerase-associated proteins in normal mice.Then,in the Alzheimer’s disease mice,UDBS was observed to decelerate telomere shortening of the cortex and myocardial tissue and to effectively improve spatial learning and memory abilities.Similarly,UDBS was found to significantly slow down telomere shortening of the cortex and peripheral blood,and improve motor and cognitive functions in aging mice.Finally,transcriptome analysis revealed that UDBS upregulated the neuroactive ligand-receptor interaction pathway.Overall,the present findings established the critical role of UDBS in delaying telomere shortening and indicated that ultrasound modulation of telomere length may constitute an effective therapeutic strategy for aging and aging-related diseases.展开更多
Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implante...Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implanted pulse generators.These facto rs necessitate invasive surgical implantation and limit potential applications.Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications.However,device miniaturization presents a serious engineering challenge.This review presents significant advancements from several groups that have overcome this challenge and developed millimetricsized nerve stimulation devices.These are based on antennas,mini-coils,magneto-electric and optoelectronic materials,or receive ultrasound power.We highlight key design elements,findings from pilot studies,and present several considerations for future applications of these devices.展开更多
Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.展开更多
Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of thi...Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.Methods:In this study,31 consecutive PD patients were treated with bilateral STN stimulation.Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale(UPDRS-ADL)at drug on(with medication)and drug off(without medication)states preoperatively and at 1,5,and 8 years postoperatively.In addition,Levodopa equivalent doses and stimulation parameters were also assessed.Results:After 8 years of STN stimulation,the UPDRS-ADL scores were improved by 4%at drug off status(P>0.05)and 22%at drug on status(P<0.05)compared with baseline;the levodopa daily doses were reduced by 28%(P<0.05)compared with baseline;the stimulation voltage and pulse width were not changed,but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up.Adverse events were observed in 6 patients,including misplacement of the electrode and skin erosion requiring further surgery.All events were resolved without permanent sequelae.2 patients died of aspiration pneumonia 6 and 7 years after surgery.Conclusions:The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.展开更多
文摘Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.
基金support by the National Nature Science Foundation of China,Nos.81830033,61761166004(both to JGZ)。
文摘There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.
基金the National Natural Science Foundation of China(No.81873467 and No.81670240).
文摘Background and Objective Since its initial report by James Parkinson in 1817,Parkinson’s disease(PD)has remained a central subject of research and clinical advancement.The disease is estimated to affect approximately 1%of adults aged 60 and above.Deep brain stimulation,emerging as an alternative therapy for end-stage cases,has offered a lifeline to numerous patients.This review aimed to analyze publications pertaining to the impact of deep brain stimulation on the motor pathway in patients with PD over the last decade.Methods Data were obtained from the Web of Science Core Collection through the library of Huazhong University of Science and Technology(China).The search strategy encompassed the following keywords:“deep brain stimulation”,“Parkinson’s disease”,“motor pathway”,and“human”,from January 1,2012,to December 1,2022.Additionally,this review visualized the findings using the Citespace software.Results The results indicated that the United States,the United Kingdom,Germany,and China were the primary contributors to this research field.University College London,Capital Medical University,and Maastricht University were the top 3 research institutions in the research area.Tom Foltynie ranked first with 6 publications,and the journals of Brain and Brain Stimulation published the greatest number of relevant articles.The prevailing research focal points in this domain,as determined by keywords“burst analysis”,“encompassed neuronal activity”,“nucleus”,“hyper direct pathway”,etc.Conclusion This study has provided a new perspective through bibliometric analysis of the deep brain stimulation therapy for treating patients with PD,which can shed light on future research to advance our comprehension of this particular field of study.
基金Natural Science Foundation of Hainan Province (No.821RC682)。
文摘Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.
文摘We conducted a systematic review of studies using non-invasive brain stimulation(NIBS: repetitive transcranial magnetic stimulation(r TMS) and transcranial direct current stimulation(t DCS)) as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury(SCI) under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI.
文摘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.
基金Project supported by the National Natural Science Foundation of China(Nos.11932003 and 11772019)。
文摘Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of Parkinson’s disease(PD).In previous studies,the development of parkinsonian network dynamics modeling has made great progress.Modeling mainly focuses on the cortex-thalamus-basal ganglia(CTBG)circuit and its sub-circuits,which helps to explore the dynamic behavior of the parkinsonian network,such as synchronization.Deep brain stimulation(DBS)is an effective strategy for the treatment of PD.At present,many studies are based on the side effects of the DBS.However,the translation from modeling results to clinical disease mitigation therapy still faces huge challenges.Here,we introduce the progress of DBS improvement.Its specific purpose is to develop novel DBS treatment methods,optimize the treatment effect of DBS for each patient,and focus on the study in closed-loop DBS.Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.
基金This study was supported in part by the Guangdong Medical Science Foundation of China,Nos.A2013252(to GXC),C2013024(to QMY)Guangdong Science and Technology Foundation of China,No.20120318018(to QMY).
文摘Deep brain stimulation of the bilateral subthalamic nucleus(STN)is a therapeutic option for patients with Parkinson’s disease(PD)in whom medical therapies have been ineffective.This retrospective cohort study analyzed the motor function of 27 patients with advanced PD,from the First Affiliated Hospital of Guangzhou Medical University,China,who received deep brain stimulation of the bilateral subthalamic nucleus and evaluated its therapeutic effects.The 10-year follow-up data of patients was analyzed in Qingyuan People’s Hospital,Sixth Affiliated Hospital of Guangzhou Medical University,China.The follow-up data were divided into two categories based on patients during levodopa treatment(on-medication)and without levodopa treatment(off-medication).Compared with baseline,the motor function of onmedication PD patients improved after deep brain stimulation of the bilateral subthalamic nucleus.Even 2 years later,the motor function of off-medication PD patients had improved.On-medication PD patients exhibited better therapeutic effects over the 5 years than offmedication PD patients.On-medication patients’akinesia,speech,postural stability,gait,and cognitive function worsened only after 5 years.These results suggest that the motor function of patients with advanced PD benefitted from treatment with deep brain stimulation of the bilateral subthalamic nucleus over a period up to 5 years.The overall therapeutic effects were more pronounced when levodopa treatment was combined with deep brain stimulation of the bilateral subthalamic nucleus.This study was approved by Institutional Review Board of Qingyuan People’s Hospital,The Sixth Affiliated Hospital of Guangzhou Medical University,China(approval No.QPH-IRB-A0140)on January 11,2018.
基金the National Natural Science Foundation of China,No.30471776
文摘BACKGROUND:Subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) has achieved good effects,but to date the mechanism of STN DBS remains poorly understood. STN DBS may increase dopamine levels or metabolic activity of the corpus striatum. OBJECTIVE:To validate the effects of STN DBS on dopamine metabolism and glucose metabolism in the corpus striatum of hemiparkinsonian monkeys using single photon emission computed tomography (SPECT) and position emission tomography (PET). DESIGN,TIME AND SETTING:A controlled animal study was performed at the Neurosurgery Laboratory,Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. METHODS:Hemiparkinsonism was induced in adult Rhesus Macaque monkeys,which exhibit similar characteristics of PD in humans,through unilateral internal carotid artery infusion of 1-methy-4-phenyl-1,2,3,6-tetrahydropyrindine. Following model establishment,stimulation electrodes were implanted in the right STN,and chronic high-frequency stimulation (60 μs pulse width,130 Hz frequency,and 1.5-2.0 V pressure) was performed. MAIN OUTCOME MEASURES:The changes in dopamine transporter (DAT),D2 receptor (D2R),and glucose metabolism in the corpus striatum following STN DBS were observed using SPECT and PET. RESULTS:SPECT examination showed that DAT specific binding in the right corpus striatum was increased at 3 months after DBS compared with prior to stimulation,and D2R specific binding in the right corpus striatum gradually decreased near levels on the left (non-electrode-implanted) side within 3 months after DBS. PET examination showed that the glucose metabolism in the right corpus striatum was markedly increased at 3 months after effective DBS. Hemiparkinsonism monkeys showed improved left limb rigidity,increased activities,and stable gait under chronic high-frequency stimulation. CONCLUSION:STN DBS increased striatal DAT,decreased D2R,and enhanced glucose metabolism,suggesting that chronic,high-frequency STN stimulation enhanced the metabolic activity of the corpus striatum,a mechanism for improving the PD symptoms of hemiparkinsonian monkeys.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.62173241 and 62171312)the Natural Science Foundation of Tianjin,China(Grant Nos.20JCQNJC01160 and 19JCZDJC36500)the financial support provided by Opening Foundation of Key Laboratory of Opto-technology and Intelligent Control(Lanzhou Jiaotong University),Ministry of Education,China(Grant No.KFKT2020-01)
文摘This paper provides an adaptive closed-loop strategy for suppressing the pathological oscillations of the basal ganglia based on a variable universe fuzzy algorithm.The pathological basal ganglia oscillations in the theta(4-9 Hz)and beta(12-35 Hz)frequency bands have been demonstrated to be associated with the tremor and rigidity/bradykinesia symptoms in Parkinson’s disease(PD).Although the clinical application of open-loop deep brain stimulation(DBS)is effective,the stimulation waveform with the fixed parameters cannot be self-adjusted as the disease progresses,and thus the stimulation effects go poor.To deal with this difficult problem,a variable universe fuzzy closed-loop strategy is proposed to modulate different PD states.We establish a cortico-basal ganglia-thalamocortical network model to simulate pathological oscillations and test the control effect.The results suggest that the proposed closed-loop control strategy can accommodate the variation of brain states and symptoms,which may become an alternative method to administrate the symptoms in PD.
文摘BACKGROUND Forniceal deep brain stimulation(DBS)has been proposed as an alternative treatment for Alzheimer's disease(AD).Previous studies on mild to moderate AD patients demonstrated improvements in cognitive functions brought about by forniceal DBS.Here,we report our longitudinal findings in one severe AD patient for whom the activities of daily living(ADL)rather than cognitive function significantly improved after 3 mo of continuous stimulation.CASE SUMMARY In 2011,a 62-year-old Chinese male with no previous history of brain injury or other neuropsychological diseases and no family history of dementia developed early symptoms of memory decline and cognitive impairment.Five years later,the symptoms had increased to the extent that they affected his daily living.He lost the ability to work as a businessman and to take care of himself.The patient was given a clinical diagnosis of probable AD and was prescribed donepezil and subsequently memantine,but no improvement in symptoms was observed.The patient then received DBS surgery.After 3 mo of continuous stimulation,the patient's ADL score decreased from 65 points to 47 points,indicating the quality of the patient's daily living improved distinctly.Other scores remained unchanged,suggesting no significant improvement in cognitive function.A follow-up positron emission tomography scan demonstrated perceivable increased glucose metabolism in the classical AD-related brain regions.CONCLUSION Based on this case we hypothesize that forniceal DBS may improve ADL through elevating regional glucose metabolism in the brain.
基金supported by Japan Society for the Promotion of Science(JSPS)Grant-in-Aid for young scientists(B)15K19984JSPS Fujita Memorial Fund for Medical Research,Takeda Science Foundation+1 种基金Uehara Memorial FoundationCentral Research Institute of Fukuoka University(No.161042)
文摘Closed-loop deep brain stimulation(DBS):DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure have been previously made.Several factors affect the DBS clinical outcomes such as lead position,programming technique,and surgical
基金Supported by Carlos Ⅲ Health Institute,No.PI16/00950 and No.PI18/00856and FEDER funds(‘A way to build Europe’).
文摘BACKGROUND Twenty years after its first use in a patient with obsessive-compulsive disorder(OCD),the results confirm that deep brain stimulation(DBS)is a promising therapy for patients with severe and resistant forms of the disorder.Nevertheless,many unknowns remain,including the optimal anatomical targets,the best stimulation parameters,the long-term(LT)effects of the therapy,and the clinical or biological factors associated with response.This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response.AIM To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD.METHODS A comprehensive search was conducted in the PubMed,Cochrane,Scopus,and ClinicalTrials.gov databases from inception to December 31,2020,using the following strategy:“(Obsessive-compulsive disorder OR OCD)AND(deep brain stimulation OR DBS).”Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool.The inclusion criteria were as follows:a main diagnosis of OCD,DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale(Y-BOCS)as primary outcome.Data were analyzed with descriptive statistics.RESULTS Forty articles identified by the search strategy met the eligibility criteria.Applying a follow-up threshold of 36 mo,29 studies(with 230 patients)provided information on short-term(ST)response to DBS in,while 11(with 155 patients)reported results on LT response.Mean follow-up period was 18.5±8.0 mo for the ST studies and 63.7±20.7 mo for the LT studies.Overall,the percentage of reduction in Y-BOCS scores was similar in ST(47.4%)and LT responses(47.2%)to DBS,but more patients in the LT reports met the criteria for response(defined as a reduction in Y-BOCS scores>35%:ST,60.6%vs LT,70.7%).According to the results,the response in the first year predicts the extent to which an OCD patient will benefit from DBS,since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation.Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients;but it is still controversial whether this improvement persists,increases or decreases in the long term.Three different patterns of LT response emerged from the analysis:49.5% of patients had good and sustained response to DBS,26.6% were non responders,and 22.5% were partial responders,who might improve at some point but experience relapses during follow-up.A significant improvement in depressive symptoms and global functionality was observed in most studies,usually(although not always)in parallel with an improvement in obsessive symptoms.Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters;however,some severe adverse events including intracranial hemorrhages and infections were also described.Hypomania was the most frequently reported psychiatric side effect.The relationship between DBS and suicide risk is still controversial and requires further study.Finally,to date,no clear clinical or biological predictors of response can be established,probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed.CONCLUSION The present review confirms that DBS is a promising therapy for patients with severe resistant OCD,providing both ST and LT evidence of efficacy.
文摘Parkinson’s disease (PD) is a neurodegenerative disease mainly caused by motor disorders, mostly occurring in middle-aged and elderly people. The incidence of PD has been increasing year by year, and up to now, PD is still an incurable disease. However, more and more data show that early implementation of deep brain stimulation and early medical, psychological, social and other interventions can significantly improve the quality of life and prolong the survival time of patients with Parkinson’s disease (PD). Mental health guidance, cognitive behavioral intervention, psychogenic therapy and scientific nursing for PD patients may improve the functional recovery after Deep Brain Stimulation (DBS) for Parkinson’s disease. This paper discusses the nursing and psychological intervention methods of deep brain stimulation (DBS) implantation in patients with Parkinson’s disease (PD), aiming to scientifically discuss the clinical effect of nursing psychological intervention and improve the quality of life in patients with Parkinson’s disease. Basic nursing and psychological cognitive behavior intervention measures for PD patients can improve the daily activity ability of PD patients, improve the outcome of PD patients, and effectively improve the satisfaction of PD patients with nursing work, which has certain clinical promotion significance.
文摘Deep brain stimulation offers an advanced means of treating Parkinson’s disease in a patient specific context. However, a considerable challenge is the process of ascertaining an optimal parameter configuration. Imperative for the deep brain stimulation parameter optimization process is the quantification of response feedback. As a significant improvement to traditional ordinal scale techniques is the advent of wearable and wireless systems. Recently conformal wearable and wireless systems with a profile on the order of a bandage have been developed. Previous research endeavors have successfully differentiated between deep brain stimulation “On” and “Off” status through quantification using wearable and wireless inertial sensor systems. However, the opportunity exists to further evolve to an objectively quantified response to an assortment of parameter configurations, such as the variation of amplitude, for the deep brain stimulation system. Multiple deep brain stimulation amplitude settings are considered inclusive of “Off” status as a baseline, 1.0 mA, 2.5 mA, and 4.0 mA. The quantified response of this assortment of amplitude settings is acquired through a conformal wearable and wireless inertial sensor system and consolidated using Python software automation to a feature set amenable for machine learning. Five machine learning algorithms are evaluated: J48 decision tree, K-nearest neighbors, support vector machine, logistic regression, and random forest. The performance of these machine learning algorithms is established based on the classification accuracy to distinguish between the deep brain stimulation amplitude settings and the time to develop the machine learning model. The support vector machine achieves the greatest classification accuracy, which is the primary performance parameter, and <span style="font-family:Verdana;">K-nearest neighbors achieves considerable classification accuracy with minimal time to develop the machine learning model.</span>
文摘Neurosurgical treatment for psychiatric disorders features a long and controversial history.This article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day,mainstream scientific deep brain stimulation(DBS).We focus on the rise,fall and possible re-emergence of psychosurgery as a therapeutic intervention today.We journey through historic indiscriminate use of prefrontal lobotomy,which evoked stern criticism from both public and professionals,through to the development of modern day DBS-performed for patients suffering from severe,treatment resistant symptoms of obsessive-compulsive disorder(OCD),epilepsy and movement disorders.We hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities,whilst simultaneously challenging any public/professional preconceptions of psychosurgery,which may indirectly be obstructing patient care.Additionally,we carried out a qualitative survey displayed in WordCloud Format,capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust,on“psychosurgery”,“prefrontal lobotomy”and“DBS”,which may well reflect wider public opinion.In summary,the article provides a brief,yet comprehensive overview of the controversial history of psychosurgery,present-day practice,and future trends of neurosurgery for psychiatric disorders.
基金supported by the National Natural Science Foundation of China(T2122023,12022410,12004410)Shenzhen Basic Science Research(JCYJ20200109105622824,JCYJ20200109110006136)+1 种基金the Natural Science Foundation of Fujian Province(2020J02063)the Xiamen Bureau of Science and Technology(3502Z20209005).
文摘Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals.The common neuromodulation techniques,including deep brain stimulation(DBS)and optogenetics,have excellent spatial resolution and depth penetration but require implementation of electrodes or optical fibers.Therefore,it is important to develop methods for noninvasive modulation of telomere length.Herein,we reported on a new method for decelerating telomere shortening using noninvasive ultrasound deep brain stimulation(UDBS).Firstly,we found that UDBS could activate the telomerase-associated proteins in normal mice.Then,in the Alzheimer’s disease mice,UDBS was observed to decelerate telomere shortening of the cortex and myocardial tissue and to effectively improve spatial learning and memory abilities.Similarly,UDBS was found to significantly slow down telomere shortening of the cortex and peripheral blood,and improve motor and cognitive functions in aging mice.Finally,transcriptome analysis revealed that UDBS upregulated the neuroactive ligand-receptor interaction pathway.Overall,the present findings established the critical role of UDBS in delaying telomere shortening and indicated that ultrasound modulation of telomere length may constitute an effective therapeutic strategy for aging and aging-related diseases.
基金funded by Western Sydney University and The University of Adelaidesupported by the Morton Cure Paralysis Fund and the Neurosurgical Research Foundation。
文摘Nerve stimulation is a rapidly developing field,demonstrating positive outcomes across several conditions.Despite potential benefits,current nerve stimulation devices are large,complicated,and are powered via implanted pulse generators.These facto rs necessitate invasive surgical implantation and limit potential applications.Reducing nerve stimulation devices to millimetric sizes would make these interventions less invasive and facilitate broader therapeutic applications.However,device miniaturization presents a serious engineering challenge.This review presents significant advancements from several groups that have overcome this challenge and developed millimetricsized nerve stimulation devices.These are based on antennas,mini-coils,magneto-electric and optoelectronic materials,or receive ultrasound power.We highlight key design elements,findings from pilot studies,and present several considerations for future applications of these devices.
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81271518).
文摘Objective:The short-term benefits of bilateral stimulation of the subthalamic nucleus(STN)in patients with advanced Parkinson’s disease(PD)are well documented,but long-term benefits are still uncertain.The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.Methods:In this study,31 consecutive PD patients were treated with bilateral STN stimulation.Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale(UPDRS-ADL)at drug on(with medication)and drug off(without medication)states preoperatively and at 1,5,and 8 years postoperatively.In addition,Levodopa equivalent doses and stimulation parameters were also assessed.Results:After 8 years of STN stimulation,the UPDRS-ADL scores were improved by 4%at drug off status(P>0.05)and 22%at drug on status(P<0.05)compared with baseline;the levodopa daily doses were reduced by 28%(P<0.05)compared with baseline;the stimulation voltage and pulse width were not changed,but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up.Adverse events were observed in 6 patients,including misplacement of the electrode and skin erosion requiring further surgery.All events were resolved without permanent sequelae.2 patients died of aspiration pneumonia 6 and 7 years after surgery.Conclusions:The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.