We are reporting the case of a 32-year-old female who had suffered from fecal incontinence(FI). She was born with an imperforate anus and a recto-vaginal fistula; she underwent repair at 6 mo of age. At 29 years of ag...We are reporting the case of a 32-year-old female who had suffered from fecal incontinence(FI). She was born with an imperforate anus and a recto-vaginal fistula; she underwent repair at 6 mo of age. At 29 years of age, she was still fecally incontinent despite extensive pelvic floor reeducation. A magnetic resonance imaging and an anal electromyography were performed. Because her symptoms were considered to be probably due to extra-sphincteric implantation of the neo-anus, a redo was performed of the recto-neo-anal intra-sphincteric anastomosis. A neurostimulator device was subsequently implanted for persistent incontinence. Solid and liquid FI resolved, and her quality of life improved markedly. Combining surgery to correct the position of the neo-anus within the anal sphincter complex and neurostimulation could thus become a new approach in cases of refractory FI for patients with imperforate anus as a newborn. Follow-up into adulthood after pediatric imperforate anus surgery should be recommended for adult patients with persistent FI.展开更多
Two emerging noninvasive neurostimulation technologies, based on electrocutaneius stimulation of the tongue (CN-NINM) and the neck (SYMPATOCORRECTION) are presented. Currently, two portable devices were developed and ...Two emerging noninvasive neurostimulation technologies, based on electrocutaneius stimulation of the tongue (CN-NINM) and the neck (SYMPATOCORRECTION) are presented. Currently, two portable devices were developed and introduced in clinical practice: PoNSTM (portable neurostimulator) and SYMPATOCOR. Both technologies are complement each other and demonstrate perspectives in various applications for purpose of neurorehabilitation and neurological symptoms management in such difficult rehabilitation areas, as traumatic brain injury, stroke, Parkinson’s disease, multiple sclerosis and many other neurological disorders.展开更多
Background:To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system(Epilcure^(TM),GenLight MedTech,Hangzhou,China)for focal drug-resistant epilepsy i...Background:To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system(Epilcure^(TM),GenLight MedTech,Hangzhou,China)for focal drug-resistant epilepsy in this study.Methods:This multicenter,before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023,involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation(RNS).The study was based on an ongoing multi-center,single-blind,randomized controlled study.Efficacy was assessed through metrics including median seizure count,seizure frequency reduction(SFR),and response rate.Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR.The postoperative quality of life,cognitive function,depression,and anxiety were evaluated as well.Results:The follow-up period for the 19 participants was 10.7±3.4 months.Seizure counts decreased significantly 6 months after device activation,with median SFR of 48%at the 6th month(M6)and 58%at M12(P<0.05).The average response rate after 13 months of treatment was 42%,with 21%(n=4)of the participants achieving seizure freedom.Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11,M12 and M13(β<0,P<0.05).No statistically significant differences were observed in patients’scores of quality of life,cognition,depression and anxiety following stimulation when compared to baseline measurements.No serious adverse events related to the devices were observed.Conclusions:The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures.However,to further validate its efficacy,larger-scale randomized controlled trials are required.Registration:Chinese Clinical Trial Registry(No.ChiCTR2200055247)展开更多
Brain-computer interface(BCI)is a revolutionary technology that can provide human beings with an alternative communication pathway between the brain and external environment.Recent technological advances have signific...Brain-computer interface(BCI)is a revolutionary technology that can provide human beings with an alternative communication pathway between the brain and external environment.Recent technological advances have significantly expanded its application to neurological rehabilitation and healthcare for patients with severe neurology disorders.Neurostimulation based on brain interface is another promising technology for neuro-modulation and intervention for patients with various neurological,psychiatric and psychological problems.展开更多
The burgeoning field of soft bioelectronics heralds a new dawn in medical treatment for neurological and psychiatric conditions,presenting innovative methods for the stimulation,inhibition,and precise sensing of neuro...The burgeoning field of soft bioelectronics heralds a new dawn in medical treatment for neurological and psychiatric conditions,presenting innovative methods for the stimulation,inhibition,and precise sensing of neuronal activities.Central to these advancements is the challenge of power supply;devices dependent on traditional batteries face limitations regarding miniaturization and require invasive surgeries for battery replacement.Triboelectric nanogenerators(TENGs),which generate power from biomechanical movements,offer a promising solution for developing self-powered neurostimulation devices without the need for an external power supply.This review delves into recent progress in TENGs,with a focus on their application in selfpowered neurostimulation systems.The utility of TENGs across various nervous systems—including the center,autonomic,and somatic nervous systems—is explored and presented,highlighting the potential for these devices to facilitate neurological treatments.By summarizing TENGs’operational details and the potential for clinical translation,this review also identifies challenges associated with the implantation and integration of neural electrodes and presents recent advances in solutions,aiming to reshape electric treatments for neurological diseases.展开更多
Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The ...Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.展开更多
Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of dia...Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.展开更多
Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulatio...Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.展开更多
Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology.Individuals with autism spectrum disorder show deficits in a variety of areas including cognitio...Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology.Individuals with autism spectrum disorder show deficits in a variety of areas including cognition,memory,attention,emotion recognition,and social skills.With no definitive treatment or cure,the main interventions for individuals with autism spectrum disorder are based on behavioral modulations.Recently,noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity,particularly in individuals with autism spectrum disorder.Preliminary evidence from small cohort studies,pilot studies,and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum disorder.However,little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial stimulation.The objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.展开更多
Neurostimulation remains the mainstay of treatment for patients with faecal incontinence who fails to respond to available conservative measures.Sacral nerve stimulation(SNS)is the main form of neurostimulation that i...Neurostimulation remains the mainstay of treatment for patients with faecal incontinence who fails to respond to available conservative measures.Sacral nerve stimulation(SNS)is the main form of neurostimulation that is in use today.Posterior tibial nerve stimulation(PTNS)-both the percutaneous and the transcutaneous routes-remains a relatively new entry in neurostimulation.Though in its infancy,PTNS holds promise to be an effective,patient friendly,safe and cheap treatment.However,presently PTNS only appears to have a minor role with SNS having the limelight in treating patients with faecal incontinence.This seems to have arisen as the strong,uniform and evidence based data on SNS remains to have been unchallenged yet by the weak,disjointed and unsupported evidence for both percutaneous and transcutaneous PTNS.The use of PTNS is slowly gaining acceptance.However,several questions remain unanswered in the delivery of PTNS.These have raised dilemmas which as long as they remain unsolved can considerably weaken the argument that PTNS could offer a viable alternative to SNS.This paper reviews available information on PTNS and focuses on these dilemmas in the light of existing evidence.展开更多
This project was intended to determine whether the preprogrammed time-varying recharge protocol for a battery incased in a neuromodulation implant can give rise to tissue temperatures that surpass a safe level or are ...This project was intended to determine whether the preprogrammed time-varying recharge protocol for a battery incased in a neuromodulation implant can give rise to tissue temperatures that surpass a safe level or are otherwise benign. The study included the development of a highly accurate model of all the thermal processes that are activated by the recharging of the battery contained within the neuromodulation implant. The model was implemented by numerical simulations performed for several realistic operating conditions. The computed spatial and temporal tissue temperature distributions were employed to estimate possible tissue damage by making use of two independent methodologies. Independent calorimeter-based experiments were performed to provide validation for the calculated rates of heat generation in the coils of the implant. Spatial and temporal tissue temperature distributions extracted from the numerical simulations revealed the thermal effects associated with several realistic operating protocols. None of the operating protocols gave rise to temperatures above 42℃. Numerical values of thermal tissue damage metrics were determined and compared with accepted values which correspond to the absence and the presence of tissue damage. The experimentally determined rate of heat generation in the implant coils validated that from electrical measurements to within 2%. Both the tissue temperature results and the thermal damage metrics found no evidence of tissue injury when time-varying preprogrammed protocols are used in the recharging of neuromodulation implant-encased batteries.展开更多
Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy t...Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy to help those patients who suffer from drug-resistant epilepsy. The goal of this surgery is to halt or reduce the intensity of seizures. This literature review aims to provide an overview of existing surgical procedures for the treatment of drug-resistant epilepsy and the degree of seizure control they provide based on available literature. Methods: Data were collected from medical journal databases, aggregators, and individual publications. The most used databases were PubMed, Medline and NCBI. Some of the keywords used to search these databases include: “drug resistant epilepsy”, “seizure control”, and “neurosurgery”. Results: Epileptic surgery is divided into resective and non-resective procedures. Studies have shown that a full resection of the epileptogenic brain area increases the probability of seizure eradication, however, the risks of postoperative impairments grow as the resection area is extended. On the other hand, patients who are unsuitable for seizure focus removal by resective surgery, such as those with multifocal seizures or overlapping epileptogenic zone with a functional cortex, may benefit from non-resective surgical options such as Vagus Nerve Stimulation and Responsive Neurostimulation. Conclusion: This literature review discusses the comprehensive treatment of epilepsy, especially the surgical treatment of drug-resistant epilepsy. The reviewed studies have shown that epilepsy surgery has promising outcomes in achieving seizure freedom/reducing seizure frequency with minimal adverse effects when performed correctly with the appropriate choice of surgical candidates.展开更多
Parkinson's Disease(PD)is a neurodegenerative condition that results in the death of dopamine-producing neurons that mainly affects the motor cortex and causes such symptoms as tremors and difficulty speaking.Whit...Parkinson's Disease(PD)is a neurodegenerative condition that results in the death of dopamine-producing neurons that mainly affects the motor cortex and causes such symptoms as tremors and difficulty speaking.White early treatments for PD included ablative and stereotactic surgeries,the precise destruction of specific brain structures,these lost favor with the emergence of levodopa in the second half of the 20th century.Nevertheless,the shortcomings of this drug,such as the reduced patient sensitivity to the treatment,sparked a new interest in surgical procedures,which in turn gave rise to the Deep Brain Stimulation(DBS)technology.In this paper,we explore the history of PD treatments with a focus on DBS,as well as the developments and advancements of the technology,including innovations in software,hardware and targeting techniques.We highlight the state of the art of PD treatment and outline future possibilities in this field.展开更多
Ultrasound(US)has emerged as a noninvasive neurostimulation method for motor control in Parkinson’s disease(PD).Previous in vivo US neuromodulation studies for PD were single-target stimulation.However,the motor symp...Ultrasound(US)has emerged as a noninvasive neurostimulation method for motor control in Parkinson’s disease(PD).Previous in vivo US neuromodulation studies for PD were single-target stimulation.However,the motor symptoms of PD are linked with neural circuit dysfunction,and multi-target stimulation is conducted in clinical treatment for PD.Thus,in the present study,we achieved multi-target US stimulation using holographic lens transducer based on the Rayleigh–Sommerfeld diffraction integral and time-reversal methods.We demonstrated that holographic US stimulation of the bilateral dorsal striatum(DS)could improve the motor function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of PD.The holographic US wave(fundamental frequency:3 MHz,pulse repetition frequency:500 Hz,duty cycle:20%,tone-burst duration:0.4 ms,sonication duration:1 s,interstimulus interval:4 s,spatial-peak temporal-average intensity:180 mw/cm2)was delivered to the bilateral DS 20 min per day for consecutive 10 d after the last injection of MPTP.Immunohistochemical c-Fos staining demonstrated that holographic US significantly increased the c-Fos-positive neurons in the bilateral DS compared with the sham group(P=0.003).Moreover,our results suggested that holographic US stimulation of the bilateral DS ameliorated motor dysfunction(P<0.05)and protected the dopaminergic(DA)neurons(P<0.001).The neuroprotective effect of holographic US was associated with the prevention of axon degeneration and the reinforcement of postsynaptic densities[growth associated protein-43(P<0.001),phosphorylated Akt(P=0.001),β3-tubulin(P<0.001),phosphorylated CRMP2(P=0.037),postsynaptic density(P=0.023)].These data suggested that holographic US-induced acoustic radiation force has the potential to achieve multi-target neuromodulation and could serve as a reliable tool for the treatment of PD.展开更多
There was much progress in the field of Neurorestoratology in the year of 2022.It included highlighting advances in understanding the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical trea...There was much progress in the field of Neurorestoratology in the year of 2022.It included highlighting advances in understanding the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology.There is still controversy about whether amyloid b-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease(AD)pathology.The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found.Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse,limited or failing bidirectional cholinergic upregulation in early cognitive impairment,or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD.Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation,immunomodulation,neurogenesis,neural network or circuitry reconstruction,neuroprotection,nervous structural repair,and neuroplasticity.Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials.However,mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke,spinal cord injury(SCI),and amyotrophic lateral sclerosis in randomized,double-blind,placebo-controlled clinical trials(RDPCTs).Clinical treatments through neurostimulation/neuromodulation and the brainecomputer/machine interface yielded positive results in AD,Parkinson's disease,stroke,SCI,cerebral palsy,and other diseases in RDPCTs.Neurorestorative surgery,pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs.Thus,this year,additional guidelines,assessment scales,and standards were set up or revised.These included guidelines of clinical neurorestorative treatments for brain trauma(2022 China version),clinical cell therapy guidelines for neurorestoration(IANR/CANR 2022),SCI or dysfunction quality of life rating scale(SCIDQLRS)(IANR 2022 version).Neurorestorative effects of varying therapeutic strategies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases.Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.展开更多
Traumatic brain injury(TBI)is a significant cause of mortality and disability globally,imposing a considerable burden on society and individuals.In recent years,neurorestorative therapies for TBI have attracted widesp...Traumatic brain injury(TBI)is a significant cause of mortality and disability globally,imposing a considerable burden on society and individuals.In recent years,neurorestorative therapies for TBI have attracted widespread attention.Despite the rapid progress in clinical neurorestorative treatments for TBI,few relevant reviews have been published.This review addresses advances in these strategies for patients with TBI,covering cellular therapies,neurostimulation therapies,brain-computer interfaces,pharmacologic therapies,and multidisciplinary therapies.This review aims to serve as a reference for clinical professionals treating patients with TBI,improving neurologic rehabilitation and outcomes for patients with TBI.展开更多
Remarkable advancements have been made in understanding the pathogenesis of Alzheimer's disease,Parkinson's disease,and other neurological disease;in our depth of understanding neurorestorative mechanisms such...Remarkable advancements have been made in understanding the pathogenesis of Alzheimer's disease,Parkinson's disease,and other neurological disease;in our depth of understanding neurorestorative mechanisms such as anti-inflammatory processes,immune regulation,neuromodulation,neovascularization/neural repair,and neuroprotection;and in clinical neurorestorative treatments.Multiple types of cell therapies have been reported,with some positive outcomes.Diverse forms of neurostimulation and neuromodulation as well as brainecomputer interfaces have shown good therapeutic outcomes in clinical applications.Further,therapeutic neurorestorative surgery and pharmaceutic therapy have been very impressive.These fundamental achievements are helpful for understanding the pathogenesis of neurological diseases and the mechanisms of neurorestoration.Patients with neurological impairments have benefited from therapeutic progress,but some of these therapies still require confirmation in higher-level randomized clinical trials.展开更多
The integration of wearable neural interfaces(WNIs)with the human nervous system has marked a significant progression,enabling progress in medical treatments and technology integration.Hydrogels,distinguished by their...The integration of wearable neural interfaces(WNIs)with the human nervous system has marked a significant progression,enabling progress in medical treatments and technology integration.Hydrogels,distinguished by their high-water content,low interfacial impedance,conductivity,adhesion,and mechanical compliance,effectively address the rigidity and biocompatibility issues common in traditional materials.This review highlights their important parameters-biocompatibility,interfacial impedance,conductivity,and adhesiveness-that are integral to their function in WNIs.The applications of hydrogels in wearable neural recording and neurostimulation are discussed in detail.Finally,the opportunities and challenges faced by hydrogels for WNIs are summarized and prospected.This review aims to offer a thorough examination of hydrogel technology’s present landscape and to encourage continued exploration and innovation.As developments progress,hydrogels are poised to revolutionize wearable neural interfaces,offering significant enhancements in healthcare and technological applications.展开更多
Conductive polymer hydrogels have greatly improved the compatibility of electronic devices with biological tissues for human–machine interfacing.Hydrogels that possess low Young's modulus,low interfacial impedanc...Conductive polymer hydrogels have greatly improved the compatibility of electronic devices with biological tissues for human–machine interfacing.Hydrogels that possess low Young's modulus,low interfacial impedance,and high tensile properties facilitate high‐quality signal transmission across dynamic biointerfaces.Direct incorporation of elastomers with conductive polymers may result in undesirable mechanical and/or electrical performance.Here,a covalent cross‐linking network and an entanglement‐driven network with conductive poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate(PEDOT:PSS)have been combined.The triple‐network conductive hydrogel shows high stretchability(with fracture strain up to 900%),low impedance(down to 91.2Ω·cm^(2)),and reversible adhesion.Importantly,ultra‐low modulus(down to 6.3 kPa)and strain‐insensitive electrical/electrochemical performance were achieved,which provides a guarantee for low current stimulation.The material design will contribute to the progression of soft and conformal bioelectronic devices,and pave the way to future implantable electronics.展开更多
This paper present a highly-integrated neurostimulator with an on-chip inductive power-recovery fron- tend and high-voltage stimulus generator. In particular, the power-recovery frontend includes a high-voltage full- ...This paper present a highly-integrated neurostimulator with an on-chip inductive power-recovery fron- tend and high-voltage stimulus generator. In particular, the power-recovery frontend includes a high-voltage full- wave rectifier （up to 100 V AC input）, high-voltage series regulators （24/5 V outputs） and a linear regulator （1.8/ 3.3 V output） with bandgap voltage reference. With the high voltage output of the series regulator, the proposed neurostimulator could deliver a considerably large current in high electrode-tissue contact impedance. This neu- rostimulator has been fabricated in a CSMC 1 μm 5/40/700 V BCD＇process and the total silicon area including pads is 5.8 mm2. Preliminary tests are successful as the neurostimulator shows good stability under a 13.56 MHz AC supply. Compared to previously reported works, our design has advantages of a wide induced voltage range （26-100 V）, high output voltage （up to 24 V） and high-level integration, which are suitable for implantable neu- rostimulators.展开更多
文摘We are reporting the case of a 32-year-old female who had suffered from fecal incontinence(FI). She was born with an imperforate anus and a recto-vaginal fistula; she underwent repair at 6 mo of age. At 29 years of age, she was still fecally incontinent despite extensive pelvic floor reeducation. A magnetic resonance imaging and an anal electromyography were performed. Because her symptoms were considered to be probably due to extra-sphincteric implantation of the neo-anus, a redo was performed of the recto-neo-anal intra-sphincteric anastomosis. A neurostimulator device was subsequently implanted for persistent incontinence. Solid and liquid FI resolved, and her quality of life improved markedly. Combining surgery to correct the position of the neo-anus within the anal sphincter complex and neurostimulation could thus become a new approach in cases of refractory FI for patients with imperforate anus as a newborn. Follow-up into adulthood after pediatric imperforate anus surgery should be recommended for adult patients with persistent FI.
文摘Two emerging noninvasive neurostimulation technologies, based on electrocutaneius stimulation of the tongue (CN-NINM) and the neck (SYMPATOCORRECTION) are presented. Currently, two portable devices were developed and introduced in clinical practice: PoNSTM (portable neurostimulator) and SYMPATOCOR. Both technologies are complement each other and demonstrate perspectives in various applications for purpose of neurorehabilitation and neurological symptoms management in such difficult rehabilitation areas, as traumatic brain injury, stroke, Parkinson’s disease, multiple sclerosis and many other neurological disorders.
基金supported by the Beijing Municipal Health Commission(No.2022-2-2011)National Natural Science Foundation of China(No.82030037)the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders(No.11000023T000002036286).
文摘Background:To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system(Epilcure^(TM),GenLight MedTech,Hangzhou,China)for focal drug-resistant epilepsy in this study.Methods:This multicenter,before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023,involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation(RNS).The study was based on an ongoing multi-center,single-blind,randomized controlled study.Efficacy was assessed through metrics including median seizure count,seizure frequency reduction(SFR),and response rate.Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR.The postoperative quality of life,cognitive function,depression,and anxiety were evaluated as well.Results:The follow-up period for the 19 participants was 10.7±3.4 months.Seizure counts decreased significantly 6 months after device activation,with median SFR of 48%at the 6th month(M6)and 58%at M12(P<0.05).The average response rate after 13 months of treatment was 42%,with 21%(n=4)of the participants achieving seizure freedom.Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11,M12 and M13(β<0,P<0.05).No statistically significant differences were observed in patients’scores of quality of life,cognition,depression and anxiety following stimulation when compared to baseline measurements.No serious adverse events related to the devices were observed.Conclusions:The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures.However,to further validate its efficacy,larger-scale randomized controlled trials are required.Registration:Chinese Clinical Trial Registry(No.ChiCTR2200055247)
文摘Brain-computer interface(BCI)is a revolutionary technology that can provide human beings with an alternative communication pathway between the brain and external environment.Recent technological advances have significantly expanded its application to neurological rehabilitation and healthcare for patients with severe neurology disorders.Neurostimulation based on brain interface is another promising technology for neuro-modulation and intervention for patients with various neurological,psychiatric and psychological problems.
基金the Vernroy Makoto Watanabe Excellence in Research Award at the UCLA Samueli School of Engineering,the Office of Naval Research Young Investigator Award(No.N00014-24-1-2065)NIH Grant(No.R01 CA287326)+4 种基金the American Heart Association for the Innovative Project Award(No.23IPA1054908)Transformational Project Award(No.23TPA1141360)Second Century Early Faculty Independence Award(No.23SCEFIA1157587)the Brain&Behavior Research Foundation Young Investigator Grant(No.30944)the NIH National Center for Advancing Translational Science UCLA CTSI(No.KL2TR001882).
文摘The burgeoning field of soft bioelectronics heralds a new dawn in medical treatment for neurological and psychiatric conditions,presenting innovative methods for the stimulation,inhibition,and precise sensing of neuronal activities.Central to these advancements is the challenge of power supply;devices dependent on traditional batteries face limitations regarding miniaturization and require invasive surgeries for battery replacement.Triboelectric nanogenerators(TENGs),which generate power from biomechanical movements,offer a promising solution for developing self-powered neurostimulation devices without the need for an external power supply.This review delves into recent progress in TENGs,with a focus on their application in selfpowered neurostimulation systems.The utility of TENGs across various nervous systems—including the center,autonomic,and somatic nervous systems—is explored and presented,highlighting the potential for these devices to facilitate neurological treatments.By summarizing TENGs’operational details and the potential for clinical translation,this review also identifies challenges associated with the implantation and integration of neural electrodes and presents recent advances in solutions,aiming to reshape electric treatments for neurological diseases.
基金supported by the National Natural Science Foundation of China,No.32130060(to XG).
文摘Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.
文摘Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.
文摘Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.
基金supported by translational grant from the HERA Foundation(to AAE).
文摘Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology.Individuals with autism spectrum disorder show deficits in a variety of areas including cognition,memory,attention,emotion recognition,and social skills.With no definitive treatment or cure,the main interventions for individuals with autism spectrum disorder are based on behavioral modulations.Recently,noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity,particularly in individuals with autism spectrum disorder.Preliminary evidence from small cohort studies,pilot studies,and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum disorder.However,little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial stimulation.The objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.
文摘Neurostimulation remains the mainstay of treatment for patients with faecal incontinence who fails to respond to available conservative measures.Sacral nerve stimulation(SNS)is the main form of neurostimulation that is in use today.Posterior tibial nerve stimulation(PTNS)-both the percutaneous and the transcutaneous routes-remains a relatively new entry in neurostimulation.Though in its infancy,PTNS holds promise to be an effective,patient friendly,safe and cheap treatment.However,presently PTNS only appears to have a minor role with SNS having the limelight in treating patients with faecal incontinence.This seems to have arisen as the strong,uniform and evidence based data on SNS remains to have been unchallenged yet by the weak,disjointed and unsupported evidence for both percutaneous and transcutaneous PTNS.The use of PTNS is slowly gaining acceptance.However,several questions remain unanswered in the delivery of PTNS.These have raised dilemmas which as long as they remain unsolved can considerably weaken the argument that PTNS could offer a viable alternative to SNS.This paper reviews available information on PTNS and focuses on these dilemmas in the light of existing evidence.
文摘This project was intended to determine whether the preprogrammed time-varying recharge protocol for a battery incased in a neuromodulation implant can give rise to tissue temperatures that surpass a safe level or are otherwise benign. The study included the development of a highly accurate model of all the thermal processes that are activated by the recharging of the battery contained within the neuromodulation implant. The model was implemented by numerical simulations performed for several realistic operating conditions. The computed spatial and temporal tissue temperature distributions were employed to estimate possible tissue damage by making use of two independent methodologies. Independent calorimeter-based experiments were performed to provide validation for the calculated rates of heat generation in the coils of the implant. Spatial and temporal tissue temperature distributions extracted from the numerical simulations revealed the thermal effects associated with several realistic operating protocols. None of the operating protocols gave rise to temperatures above 42℃. Numerical values of thermal tissue damage metrics were determined and compared with accepted values which correspond to the absence and the presence of tissue damage. The experimentally determined rate of heat generation in the implant coils validated that from electrical measurements to within 2%. Both the tissue temperature results and the thermal damage metrics found no evidence of tissue injury when time-varying preprogrammed protocols are used in the recharging of neuromodulation implant-encased batteries.
文摘Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy to help those patients who suffer from drug-resistant epilepsy. The goal of this surgery is to halt or reduce the intensity of seizures. This literature review aims to provide an overview of existing surgical procedures for the treatment of drug-resistant epilepsy and the degree of seizure control they provide based on available literature. Methods: Data were collected from medical journal databases, aggregators, and individual publications. The most used databases were PubMed, Medline and NCBI. Some of the keywords used to search these databases include: “drug resistant epilepsy”, “seizure control”, and “neurosurgery”. Results: Epileptic surgery is divided into resective and non-resective procedures. Studies have shown that a full resection of the epileptogenic brain area increases the probability of seizure eradication, however, the risks of postoperative impairments grow as the resection area is extended. On the other hand, patients who are unsuitable for seizure focus removal by resective surgery, such as those with multifocal seizures or overlapping epileptogenic zone with a functional cortex, may benefit from non-resective surgical options such as Vagus Nerve Stimulation and Responsive Neurostimulation. Conclusion: This literature review discusses the comprehensive treatment of epilepsy, especially the surgical treatment of drug-resistant epilepsy. The reviewed studies have shown that epilepsy surgery has promising outcomes in achieving seizure freedom/reducing seizure frequency with minimal adverse effects when performed correctly with the appropriate choice of surgical candidates.
文摘Parkinson's Disease(PD)is a neurodegenerative condition that results in the death of dopamine-producing neurons that mainly affects the motor cortex and causes such symptoms as tremors and difficulty speaking.White early treatments for PD included ablative and stereotactic surgeries,the precise destruction of specific brain structures,these lost favor with the emergence of levodopa in the second half of the 20th century.Nevertheless,the shortcomings of this drug,such as the reduced patient sensitivity to the treatment,sparked a new interest in surgical procedures,which in turn gave rise to the Deep Brain Stimulation(DBS)technology.In this paper,we explore the history of PD treatments with a focus on DBS,as well as the developments and advancements of the technology,including innovations in software,hardware and targeting techniques.We highlight the state of the art of PD treatment and outline future possibilities in this field.
基金supported,in part,by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0930000)the National Natural Science Foundation of China(nos.T2122023,U23A20479,12227809,and 12104478)+1 种基金the Natural Science Foundation of Guangdong Province(no.202381515040008)Shenzhen Basic Science Research(nos.JCYJ20220818101608018,20231123154444001,and 20220812171109001).
文摘Ultrasound(US)has emerged as a noninvasive neurostimulation method for motor control in Parkinson’s disease(PD).Previous in vivo US neuromodulation studies for PD were single-target stimulation.However,the motor symptoms of PD are linked with neural circuit dysfunction,and multi-target stimulation is conducted in clinical treatment for PD.Thus,in the present study,we achieved multi-target US stimulation using holographic lens transducer based on the Rayleigh–Sommerfeld diffraction integral and time-reversal methods.We demonstrated that holographic US stimulation of the bilateral dorsal striatum(DS)could improve the motor function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of PD.The holographic US wave(fundamental frequency:3 MHz,pulse repetition frequency:500 Hz,duty cycle:20%,tone-burst duration:0.4 ms,sonication duration:1 s,interstimulus interval:4 s,spatial-peak temporal-average intensity:180 mw/cm2)was delivered to the bilateral DS 20 min per day for consecutive 10 d after the last injection of MPTP.Immunohistochemical c-Fos staining demonstrated that holographic US significantly increased the c-Fos-positive neurons in the bilateral DS compared with the sham group(P=0.003).Moreover,our results suggested that holographic US stimulation of the bilateral DS ameliorated motor dysfunction(P<0.05)and protected the dopaminergic(DA)neurons(P<0.001).The neuroprotective effect of holographic US was associated with the prevention of axon degeneration and the reinforcement of postsynaptic densities[growth associated protein-43(P<0.001),phosphorylated Akt(P=0.001),β3-tubulin(P<0.001),phosphorylated CRMP2(P=0.037),postsynaptic density(P=0.023)].These data suggested that holographic US-induced acoustic radiation force has the potential to achieve multi-target neuromodulation and could serve as a reliable tool for the treatment of PD.
文摘There was much progress in the field of Neurorestoratology in the year of 2022.It included highlighting advances in understanding the pathogenesis of neurological diseases,neurorestorative mechanisms,and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology.There is still controversy about whether amyloid b-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease(AD)pathology.The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found.Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse,limited or failing bidirectional cholinergic upregulation in early cognitive impairment,or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD.Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation,immunomodulation,neurogenesis,neural network or circuitry reconstruction,neuroprotection,nervous structural repair,and neuroplasticity.Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials.However,mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke,spinal cord injury(SCI),and amyotrophic lateral sclerosis in randomized,double-blind,placebo-controlled clinical trials(RDPCTs).Clinical treatments through neurostimulation/neuromodulation and the brainecomputer/machine interface yielded positive results in AD,Parkinson's disease,stroke,SCI,cerebral palsy,and other diseases in RDPCTs.Neurorestorative surgery,pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs.Thus,this year,additional guidelines,assessment scales,and standards were set up or revised.These included guidelines of clinical neurorestorative treatments for brain trauma(2022 China version),clinical cell therapy guidelines for neurorestoration(IANR/CANR 2022),SCI or dysfunction quality of life rating scale(SCIDQLRS)(IANR 2022 version).Neurorestorative effects of varying therapeutic strategies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases.Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.
基金supported by the Public Welfare Science and Technology Project of Ningbo(2022S029)the National Natural Science Foundation of China(U23A20334).
文摘Traumatic brain injury(TBI)is a significant cause of mortality and disability globally,imposing a considerable burden on society and individuals.In recent years,neurorestorative therapies for TBI have attracted widespread attention.Despite the rapid progress in clinical neurorestorative treatments for TBI,few relevant reviews have been published.This review addresses advances in these strategies for patients with TBI,covering cellular therapies,neurostimulation therapies,brain-computer interfaces,pharmacologic therapies,and multidisciplinary therapies.This review aims to serve as a reference for clinical professionals treating patients with TBI,improving neurologic rehabilitation and outcomes for patients with TBI.
文摘Remarkable advancements have been made in understanding the pathogenesis of Alzheimer's disease,Parkinson's disease,and other neurological disease;in our depth of understanding neurorestorative mechanisms such as anti-inflammatory processes,immune regulation,neuromodulation,neovascularization/neural repair,and neuroprotection;and in clinical neurorestorative treatments.Multiple types of cell therapies have been reported,with some positive outcomes.Diverse forms of neurostimulation and neuromodulation as well as brainecomputer interfaces have shown good therapeutic outcomes in clinical applications.Further,therapeutic neurorestorative surgery and pharmaceutic therapy have been very impressive.These fundamental achievements are helpful for understanding the pathogenesis of neurological diseases and the mechanisms of neurorestoration.Patients with neurological impairments have benefited from therapeutic progress,but some of these therapies still require confirmation in higher-level randomized clinical trials.
基金support from the Alzheimer’s Association New to the Field(AARG-NTF)research grant,DAPRA REM REST program,UT Austin Proof of Concept Award,Texas Health Catalyst Award,and NIH Maximizing Investigators’Research Award(MIRA)(R35)grant(Grant Number:5R35GM147408-03).
文摘The integration of wearable neural interfaces(WNIs)with the human nervous system has marked a significant progression,enabling progress in medical treatments and technology integration.Hydrogels,distinguished by their high-water content,low interfacial impedance,conductivity,adhesion,and mechanical compliance,effectively address the rigidity and biocompatibility issues common in traditional materials.This review highlights their important parameters-biocompatibility,interfacial impedance,conductivity,and adhesiveness-that are integral to their function in WNIs.The applications of hydrogels in wearable neural recording and neurostimulation are discussed in detail.Finally,the opportunities and challenges faced by hydrogels for WNIs are summarized and prospected.This review aims to offer a thorough examination of hydrogel technology’s present landscape and to encourage continued exploration and innovation.As developments progress,hydrogels are poised to revolutionize wearable neural interfaces,offering significant enhancements in healthcare and technological applications.
基金Financial support by the National Key Research and Development Program of China(No.2022YFF1202902)the National Natural Science Foundation of China(Nos.52273192 and 52121002)the Haihe Laboratory of Sustainable Chemical Transformations are gratefully acknowledged.
文摘Conductive polymer hydrogels have greatly improved the compatibility of electronic devices with biological tissues for human–machine interfacing.Hydrogels that possess low Young's modulus,low interfacial impedance,and high tensile properties facilitate high‐quality signal transmission across dynamic biointerfaces.Direct incorporation of elastomers with conductive polymers may result in undesirable mechanical and/or electrical performance.Here,a covalent cross‐linking network and an entanglement‐driven network with conductive poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate(PEDOT:PSS)have been combined.The triple‐network conductive hydrogel shows high stretchability(with fracture strain up to 900%),low impedance(down to 91.2Ω·cm^(2)),and reversible adhesion.Importantly,ultra‐low modulus(down to 6.3 kPa)and strain‐insensitive electrical/electrochemical performance were achieved,which provides a guarantee for low current stimulation.The material design will contribute to the progression of soft and conformal bioelectronic devices,and pave the way to future implantable electronics.
基金Project supported by the National Natural Science Foundation of China(Nos.61076023,61178051)the National Basic Research Program of China(No.2011CB933203)the High-Tech-Program of China(No.2012AA030308)
文摘This paper present a highly-integrated neurostimulator with an on-chip inductive power-recovery fron- tend and high-voltage stimulus generator. In particular, the power-recovery frontend includes a high-voltage full- wave rectifier （up to 100 V AC input）, high-voltage series regulators （24/5 V outputs） and a linear regulator （1.8/ 3.3 V output） with bandgap voltage reference. With the high voltage output of the series regulator, the proposed neurostimulator could deliver a considerably large current in high electrode-tissue contact impedance. This neu- rostimulator has been fabricated in a CSMC 1 μm 5/40/700 V BCD＇process and the total silicon area including pads is 5.8 mm2. Preliminary tests are successful as the neurostimulator shows good stability under a 13.56 MHz AC supply. Compared to previously reported works, our design has advantages of a wide induced voltage range （26-100 V）, high output voltage （up to 24 V） and high-level integration, which are suitable for implantable neu- rostimulators.
