Neuromodulation is mediated by neurotransmitters that typically act on G-protein-coupled receptors.It can confer behavioural flexibility by modifying the functional properties of anatomically hard-wired neural circuit...Neuromodulation is mediated by neurotransmitters that typically act on G-protein-coupled receptors.It can confer behavioural flexibility by modifying the functional properties of anatomically hard-wired neural circuits.Single neuromodulators generally have divergent cellular and synaptic effects（Harris-Warrick and Johnson,2010）,and different modulators,展开更多
Treatment for disorders of consciousness （DOCs） is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potenti...Treatment for disorders of consciousness （DOCs） is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potential treatment. Multiple neuromodulation therapies have been applied. This article reviews the most relevant studies in the literature in order to describe a clear picture of the current state of neuromodulation therapies that could be used to treat DOC patients. Both invasive and noninvasive brain stimulation is discussed. Significant behavioral improvements in prolonged DOCs under neuromodulation therapies are rare. The efficacy of various such therapies remains a matter of debate. Further clinical investigations of existing techniques in larger samples properly controlling for spontaneous recovery are needed, and new approaches are awaited.展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modalit...Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury.Based on similar principles,this review aims to explore the potential of optical and acoustic neuromodulation techniques,emphasizing their benefits in the context of spinal cord injury.Photoacoustic imaging,renowned for its noninvasive nature,high-resolution capabilities,and cost-effectiveness,is well recognized for its role in early diagnosis,dynamic monitoring,and surgical guidance in stem cell therapies for spinal cord injury.Moreover,photoacoustodynamic therapy offers multiple pathways for tissue regeneration.Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation,while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system,introducing an innovative paradigm for nerve system disorder management.Collectively,these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury,with the potential to significantly enhance nerve function remodeling and improve patient outcomes.展开更多
Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.展开更多
Background:Reviving patients with prolonged disorders of consciousness(DOCs)has always been focused and challenging in medical research.Owing to the limited effectiveness of available medicine,recent research has incr...Background:Reviving patients with prolonged disorders of consciousness(DOCs)has always been focused and challenging in medical research.Owing to the limited effectiveness of available medicine,recent research has increasingly turned towards neuromodulatory therapies,involving the stimulation of neural circuits.We summarised the progression of research regarding neuromodulatory therapies in the field of DOCs,compared the differences among different studies,in an attempt to explore optimal stimulation patterns and parameters,and analyzed the major limitations of the relevant studies to facilitate future research.Methods:We performed a search in the PubMed database,using the concepts of DOCs and neuromodulation.Inclusion criteria were:articles in English,published after 2002,and reporting clinical trials of neuromodulatory therapies in human patients with DOCs.Results:Overall,187 published articles met the search criteria,and 60 articles met the inclusion criteria.There are differences among these studies regarding the clinical efficacies of neurostimulation techniques for patients with DOCs,and large-sample studies are still lacking.Conclusions:Neuromodulatory techniques were used as trial therapies for DOCs wherein their curative effects were controversial.The difficulties in detecting residual consciousness,the confounding effect between the natural course of the disease and therapeutic effect,and the heterogeneity across patients are the major limitations.Large-sample,well-designed studies,and innovations for both treatment and assessment are anticipated in future research.展开更多
Gastroparesis is a severe diabetic complication,caused by a progressive multifactorial enteric neuropathy.To make an early diagnosis in patients at risk of diabetic gastroparesis is crucial for slow down its progressi...Gastroparesis is a severe diabetic complication,caused by a progressive multifactorial enteric neuropathy.To make an early diagnosis in patients at risk of diabetic gastroparesis is crucial for slow down its progression towards full-blown disease source of further complications and requesting effective,but unsafe,drugs as well as invasive surgical treatments.This aim can be achieved by detecting its first signal represented by the gastric emptying(GE)delay,by using,among the tests to measure GE,the simple,safe,reliable,and easily available one,that is realtime ultrasonography,possibly done annually.Once the GE delay has been identified,it is necessary to evaluate with endoluminal functional lumen imaging probe or manometry whether it depends on pylorospasm,which should be treated by means of non-surgical endoscopic therapies.If,instead,it depends on initial gastropathy,detected by electrogastrograhic body surface gastric mapping,it should be treated with the safest prokinetic drugs and with the newly emerging treatments,thus distancing heavy medical and surgical treatments,while waiting for future solutions.展开更多
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.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
Fecal incontinence is a common condition that can significantly impact patients’quality of life.Obstetric anal sphincter injury and anorectal surgeries are common etiologies.Endoanal ultrasound and anorectal manometr...Fecal incontinence is a common condition that can significantly impact patients’quality of life.Obstetric anal sphincter injury and anorectal surgeries are common etiologies.Endoanal ultrasound and anorectal manometry are important diagnostic tools for evaluating patients.There are various treatment options,including diet,lifestyle modifications,drugs,biofeedback therapy,tibial and sacral nerve neuromodulation therapy,and surgery.In this editorial,we will discuss current controversies and novel approaches to fecal incontinence.Screening for asymptomatic anal sphincter defects after obstetric anal sphincter injury and in patients with inflammatory bowel disease is not generally recommended,but may be helpful in selected patients.The Garg incontinence score is a new score that includes the assessment of solid,liquid,flatus,mucous,stress and urge fecal incontinence.Novel tests such as translumbosacral anorectal magnetic stimulation and novel therapies such as translumbosacral neuromodulation therapy are promising diagnostic and treatment options,for both fecal incontinence and neuropathy.Home biofeedback therapy can overcome some limitations of the office-based therapy.Skeletal muscle-derived cell implantation of the external anal sphincter has been further studied as a possible treatment option.Sacral neuromodulation may be useful in scleroderma,congenital fecal incontinence and inflammatory bowel disease but merits further study.展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
Progressive neurodegenerative diseases(NDs)that lack effective disease-modifying treatments,including Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington's dis...Progressive neurodegenerative diseases(NDs)that lack effective disease-modifying treatments,including Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington's disease(HD),represent significant global health challenges.In recent years,key research findings have included the role of neuroinflammation driven by microglia and astrocytes,the impact of genetic mutations,and the importance of autophagy and mitochondrial quality control in maintaining neuronal health.In this review,we summarize recent advancements of the pathogenesis of NDs,the cellular and animal models that have provided valuable insights into disease mechanisms,and the development of blood-based biomarkers for early diagnosis and monitoring of disease progression.We also highlight emerging neurorestorative therapeutic strategies involving stem cell therapy,antisense oligonucleotides,and induced pluripotent stem cells.Additionally,we cover recent clinical trials of promising drugs,such as lecanemab and donanemab for AD,and tavapadon for PD.Finally,we propose future research directions,emphasizing the need for combination therapies that target multiple pathways,the development of more precise animal models,and the integration of nanotechnology for improved drug delivery across the blood–brain barrier.展开更多
Depression is a multifaceted disorder with a largely unresolved etiology influenced by a complex interplay of pathogenic factors.Despite decades of research,it remains a major condition that significantly diminishes p...Depression is a multifaceted disorder with a largely unresolved etiology influenced by a complex interplay of pathogenic factors.Despite decades of research,it remains a major condition that significantly diminishes patients’quality of life.Advances in optogenetics have introduced a powerful tool for exploring the neural mechanisms underlying depression.By selectively expressing optogenes in specific cell types in mice,researchers can study the roles of these cells through targeted light stimulation,offering new insights into central nervous system disorders.The use of viral vectors to express opsins in distinct neuronal subtypes enables precise activation or inhibition of these neurons via light.When combined with behavioral,morphological,and electrophysiological analyses,optogenetics provides an invaluable approach to investigating the neural mechanisms of psychiatric conditions.This review synthesizes current research on the application of optogenetics to understand the mechanisms of depression.This study aims to enhance our knowledge of optogenetic strategies for regulating depression and advancing antidepressant research.展开更多
Dysfunction of the interoceptive system is recognized as an important component of clinical symptoms,including anxiety,depression,psychosis,and other mental disorders.Non-invasive neuromodulation is an emerging clinic...Dysfunction of the interoceptive system is recognized as an important component of clinical symptoms,including anxiety,depression,psychosis,and other mental disorders.Non-invasive neuromodulation is an emerging clinical intervention approach,and over the past decade,research on non-invasive neuromodulation aimed at regulating interoception has rapidly developed.This review first outlines the pathways of interoceptive signals and assessment methods,then summarizes the interoceptive abnormalities in psychiatric disorders and current studies for non-invasive neuromodulation targeting interoception,including intervention modes,target sites,interoceptive measures,and potential neurobiological mechanisms.Finally,we discuss significant research challenges and future directions.展开更多
Stroke remains a leading cause of long-term disability worldwide.There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery.Transc...Stroke remains a leading cause of long-term disability worldwide.There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery.Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke.However,previously published research has only investigated a narrow range of stimulation settings and indications.In this review,we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials.We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke,highlighting their indications,parameter settings,scope,and limitations.We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation,focusing on critical aspects such as stimulation settings,target groups,biomarkers,and integration with rehabilitation interventions.展开更多
Vision restoration presents a considerable challenge in the realm of regenerative medicine,while recent progress in ultrasound stimulation has displayed potential as a non-invasive therapeutic approach.This narrative ...Vision restoration presents a considerable challenge in the realm of regenerative medicine,while recent progress in ultrasound stimulation has displayed potential as a non-invasive therapeutic approach.This narrative review offers a comprehensive overview of current research on ultrasound-stimulated neuromodulation,emphasizing its potential as a treatment modality for various nerve injuries.By examining of the efficacy of different types of ultrasound stimulation in modulating peripheral and optic nerves,we can delve into their underlying molecular mechanisms.Furthermore,the review underscores the potential of sonogenetics in vision restoration,which involves leveraging pharmacological and genetic manipulations to inhibit or enhance the expression of related mechanosensitive channels,thereby modulating the strength of the ultrasound response.We also address how methods such as viral transcription can be utilized to render specific neurons or organs highly responsive to ultrasound,leading to significantly improved therapeutic outcomes.展开更多
Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While sympto...Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.展开更多
BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder,with limited evidence for pharmacotherapy.Treatment typically involves medication,cognitive behavioral therapy,and behavioral interventions.Re...BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder,with limited evidence for pharmacotherapy.Treatment typically involves medication,cognitive behavioral therapy,and behavioral interventions.Recently,transcranial magnetic stimulation(TMS)has emerged as a potential treatment strategy.AIM To assess the role of TMS in treating trichotillomania.METHODS A systematic search using specific terms was done in PubMed and Scopus databases for articles published until May 17,2024,related to trichotillomania and TMS.The search included randomized controlled trials,open-label studies,case series,case reports,and retrospective chart reviews,following the Preferred Items for Systematic Reviews and Meta-Analysis guideline.RESULTS We identified 32 articles(6 in PubMed and 26 in Scopus).After removing duplicates and articles that did not meet the selection criteria,we conducted a final analysis of four articles.These included one retrospective study,two case series,and one case study,with a total of 22 patients diagnosed with trichotillomania enrolled across all four studies.The brain areas targeted were the supplementary motor area(SMA),pre-SMA,and left dorsolateral prefrontal cortex.The studies reported an improvement in the severity of symptoms of trichotillomania in the majority of patients with negligible side effects.Nevertheless,it is important to note that the existing studies are mostly of low to moderate quality.CONCLUSION Early evidence suggests repetitive TMS and accelerated continuous theta burst stimulation can help treat trichotillomania adjunctively to other treatments.展开更多
Parkinson’s disease patients,in addition to typical motor symptoms,often experience various psychological symptoms,including depression,anxiety,cognitive impairment,impulse control disorders,and psychotic symptoms.Th...Parkinson’s disease patients,in addition to typical motor symptoms,often experience various psychological symptoms,including depression,anxiety,cognitive impairment,impulse control disorders,and psychotic symptoms.These symptoms severely affect patients’quality of life and may even cause a greater disease burden than motor symptoms.This review focuses on the application progress of transcranial magnetic stimulation(TMS)as a non-invasive neuromodulation technique in the treatment of psychological symptoms in Parkinson’s disease.Studies have shown that repetitive TMS(rTMS)has significant improvement effects on Parkinson’s disease-related depressive symptoms,with mechanisms possibly related to the regulation of the prefrontal-striatal dopamine pathway and the promotion of neuroplasticity.For anxiety symptoms,continuous theta burst stimulation has shown potential in indirect regulation of the amygdala and hippocampal regions.For cognitive impairment,high-frequency rTMS applied to the dorsolateral prefrontal cortex can improve executive function deficits,while bilateral coordinated stimulation protocols help enhance attention and memory functions.For impulse control disorders in Parkinson’s disease patients,inhibitory stimulation applied to the orbitofrontal cortex can alleviate pathological gambling and compulsive behaviors.In terms of sleep disorders,TMS has also shown potential efficacy in regulating circadian rhythms and improving rapid eye movement sleep behavior disorder.However,current research still has limitations such as small sample sizes,non-standardized stimulation protocols,and insufficient evaluation of long-term efficacy.Future research directions should focus on optimizing stimulation parameters,exploring individualized treatment protocols,integrating multimodal imaging assessments,and conducting large-sample randomized controlled trials to clarify the clinical application value of TMS in the rehabilitation of psychological symptoms in Parkinson’s disease,providing new approaches for the comprehensive management of this common neurodegenerative disease.展开更多
Closed-loop neuromodulation,especially using the phase of the electroencephalography(EEG)rhythm to assess the real-time brain state and optimize the brain stimulation process,is becoming a hot research topic.Because t...Closed-loop neuromodulation,especially using the phase of the electroencephalography(EEG)rhythm to assess the real-time brain state and optimize the brain stimulation process,is becoming a hot research topic.Because the EEG signal is non-stationary,the commonly used EEG phase-based prediction methods have large variances,which may reduce the accuracy of the phase prediction.In this study,we proposed a machine learning-based EEG phase prediction network,which we call EEG phase prediction network(EPN),to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data.We verified the performance of EPN on pre-recorded data,simulated EEG data,and a real-time experiment.Compared with widely used state-of-the-art models(optimized multi-layer filter architecture,auto-regress,and educated temporal prediction),EPN achieved the lowest variance and the greatest accuracy.Thus,the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.展开更多
文摘Neuromodulation is mediated by neurotransmitters that typically act on G-protein-coupled receptors.It can confer behavioural flexibility by modifying the functional properties of anatomically hard-wired neural circuits.Single neuromodulators generally have divergent cellular and synaptic effects（Harris-Warrick and Johnson,2010）,and different modulators,
基金supported by the National Natural Science Foundation of China (81771128)the Beijing Municipal Science & Technology Commission (Z171100001017162 and Z161100000516165)
文摘Treatment for disorders of consciousness （DOCs） is still a Gordian knot. Evidence-based guidelines on the treatment of DOC patients are not currently available, while neuromodulation techniques are seen as a potential treatment. Multiple neuromodulation therapies have been applied. This article reviews the most relevant studies in the literature in order to describe a clear picture of the current state of neuromodulation therapies that could be used to treat DOC patients. Both invasive and noninvasive brain stimulation is discussed. Significant behavioral improvements in prolonged DOCs under neuromodulation therapies are rare. The efficacy of various such therapies remains a matter of debate. Further clinical investigations of existing techniques in larger samples properly controlling for spontaneous recovery are needed, and new approaches are awaited.
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
基金supported by the National Key R&D Program of China,No.2023YFC2509700the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund,No.L232141the Research and Application of Clinical Characteristic Diagnosis and Treatment Program,No.Z221100007422019(all to WD)。
文摘Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury.Based on similar principles,this review aims to explore the potential of optical and acoustic neuromodulation techniques,emphasizing their benefits in the context of spinal cord injury.Photoacoustic imaging,renowned for its noninvasive nature,high-resolution capabilities,and cost-effectiveness,is well recognized for its role in early diagnosis,dynamic monitoring,and surgical guidance in stem cell therapies for spinal cord injury.Moreover,photoacoustodynamic therapy offers multiple pathways for tissue regeneration.Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation,while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system,introducing an innovative paradigm for nerve system disorder management.Collectively,these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury,with the potential to significantly enhance nerve function remodeling and improve patient outcomes.
基金supported by the National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
基金National Natural Science Foundation of China(No.81870817)Fundamental Research Funds for the Central Universities(No.2019-XZZX-001-01-02)Key Realm R&D Program of Guangzhou(No.202007030005)。
文摘Background:Reviving patients with prolonged disorders of consciousness(DOCs)has always been focused and challenging in medical research.Owing to the limited effectiveness of available medicine,recent research has increasingly turned towards neuromodulatory therapies,involving the stimulation of neural circuits.We summarised the progression of research regarding neuromodulatory therapies in the field of DOCs,compared the differences among different studies,in an attempt to explore optimal stimulation patterns and parameters,and analyzed the major limitations of the relevant studies to facilitate future research.Methods:We performed a search in the PubMed database,using the concepts of DOCs and neuromodulation.Inclusion criteria were:articles in English,published after 2002,and reporting clinical trials of neuromodulatory therapies in human patients with DOCs.Results:Overall,187 published articles met the search criteria,and 60 articles met the inclusion criteria.There are differences among these studies regarding the clinical efficacies of neurostimulation techniques for patients with DOCs,and large-sample studies are still lacking.Conclusions:Neuromodulatory techniques were used as trial therapies for DOCs wherein their curative effects were controversial.The difficulties in detecting residual consciousness,the confounding effect between the natural course of the disease and therapeutic effect,and the heterogeneity across patients are the major limitations.Large-sample,well-designed studies,and innovations for both treatment and assessment are anticipated in future research.
文摘Gastroparesis is a severe diabetic complication,caused by a progressive multifactorial enteric neuropathy.To make an early diagnosis in patients at risk of diabetic gastroparesis is crucial for slow down its progression towards full-blown disease source of further complications and requesting effective,but unsafe,drugs as well as invasive surgical treatments.This aim can be achieved by detecting its first signal represented by the gastric emptying(GE)delay,by using,among the tests to measure GE,the simple,safe,reliable,and easily available one,that is realtime ultrasonography,possibly done annually.Once the GE delay has been identified,it is necessary to evaluate with endoluminal functional lumen imaging probe or manometry whether it depends on pylorospasm,which should be treated by means of non-surgical endoscopic therapies.If,instead,it depends on initial gastropathy,detected by electrogastrograhic body surface gastric mapping,it should be treated with the safest prokinetic drugs and with the newly emerging treatments,thus distancing heavy medical and surgical treatments,while waiting for future solutions.
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
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Fecal incontinence is a common condition that can significantly impact patients’quality of life.Obstetric anal sphincter injury and anorectal surgeries are common etiologies.Endoanal ultrasound and anorectal manometry are important diagnostic tools for evaluating patients.There are various treatment options,including diet,lifestyle modifications,drugs,biofeedback therapy,tibial and sacral nerve neuromodulation therapy,and surgery.In this editorial,we will discuss current controversies and novel approaches to fecal incontinence.Screening for asymptomatic anal sphincter defects after obstetric anal sphincter injury and in patients with inflammatory bowel disease is not generally recommended,but may be helpful in selected patients.The Garg incontinence score is a new score that includes the assessment of solid,liquid,flatus,mucous,stress and urge fecal incontinence.Novel tests such as translumbosacral anorectal magnetic stimulation and novel therapies such as translumbosacral neuromodulation therapy are promising diagnostic and treatment options,for both fecal incontinence and neuropathy.Home biofeedback therapy can overcome some limitations of the office-based therapy.Skeletal muscle-derived cell implantation of the external anal sphincter has been further studied as a possible treatment option.Sacral neuromodulation may be useful in scleroderma,congenital fecal incontinence and inflammatory bowel disease but merits further study.
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
基金Project of Hubei Key Laboratory of Cognitive and Affective Disorders(HBCAD2024-13).
文摘Progressive neurodegenerative diseases(NDs)that lack effective disease-modifying treatments,including Alzheimer's disease(AD),Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),and Huntington's disease(HD),represent significant global health challenges.In recent years,key research findings have included the role of neuroinflammation driven by microglia and astrocytes,the impact of genetic mutations,and the importance of autophagy and mitochondrial quality control in maintaining neuronal health.In this review,we summarize recent advancements of the pathogenesis of NDs,the cellular and animal models that have provided valuable insights into disease mechanisms,and the development of blood-based biomarkers for early diagnosis and monitoring of disease progression.We also highlight emerging neurorestorative therapeutic strategies involving stem cell therapy,antisense oligonucleotides,and induced pluripotent stem cells.Additionally,we cover recent clinical trials of promising drugs,such as lecanemab and donanemab for AD,and tavapadon for PD.Finally,we propose future research directions,emphasizing the need for combination therapies that target multiple pathways,the development of more precise animal models,and the integration of nanotechnology for improved drug delivery across the blood–brain barrier.
基金funded by the Natural Science Foundation of China(No.82305049).
文摘Depression is a multifaceted disorder with a largely unresolved etiology influenced by a complex interplay of pathogenic factors.Despite decades of research,it remains a major condition that significantly diminishes patients’quality of life.Advances in optogenetics have introduced a powerful tool for exploring the neural mechanisms underlying depression.By selectively expressing optogenes in specific cell types in mice,researchers can study the roles of these cells through targeted light stimulation,offering new insights into central nervous system disorders.The use of viral vectors to express opsins in distinct neuronal subtypes enables precise activation or inhibition of these neurons via light.When combined with behavioral,morphological,and electrophysiological analyses,optogenetics provides an invaluable approach to investigating the neural mechanisms of psychiatric conditions.This review synthesizes current research on the application of optogenetics to understand the mechanisms of depression.This study aims to enhance our knowledge of optogenetic strategies for regulating depression and advancing antidepressant research.
基金supported by grants from the National Natural Science Foundation of China(82101582)the Shanghai Science and Technology Committee(22Y11903600 and 23Y11906000)the Shanghai Municipal Health Commission(202240266).
文摘Dysfunction of the interoceptive system is recognized as an important component of clinical symptoms,including anxiety,depression,psychosis,and other mental disorders.Non-invasive neuromodulation is an emerging clinical intervention approach,and over the past decade,research on non-invasive neuromodulation aimed at regulating interoception has rapidly developed.This review first outlines the pathways of interoceptive signals and assessment methods,then summarizes the interoceptive abnormalities in psychiatric disorders and current studies for non-invasive neuromodulation targeting interoception,including intervention modes,target sites,interoceptive measures,and potential neurobiological mechanisms.Finally,we discuss significant research challenges and future directions.
基金an Association of British Neurologists Doctoral Research Fellowship co-funded by the Berkeley Foundation and the Stroke Associationsupported by a NIHR Academic Clinical Lectureship in Neurology CL-2020-04-004 NIHR+3 种基金supported by the NIHR Sheffield Biomedical Research Centre(BRC)NIHR Sheffield Clinical Research Facility(CRF)supported by NIHR EME Project Grant NIHR133169funded by Alzheimer’s Research UK Senior Research Fellowship(ARUK-SRF2017B-1)。
文摘Stroke remains a leading cause of long-term disability worldwide.There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery.Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke.However,previously published research has only investigated a narrow range of stimulation settings and indications.In this review,we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials.We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke,highlighting their indications,parameter settings,scope,and limitations.We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation,focusing on critical aspects such as stimulation settings,target groups,biomarkers,and integration with rehabilitation interventions.
基金supported by R01EY032229(Biomechanical Mapping of the Optic Nerve Head and Peripapillary Sclera Using High Frequency Ultrasonic Elastography)R01EY028662(High-resolution Elastographic Assessment of the Optic Nerve Head)+2 种基金R01EY030126(Non-invasive Ultrasound Stimulated Retinal Prosthesis)(to QZ)Unrestricted Grant to the Department of Ophthalmology from Research to Prevent Blindness,New York,NY(to MSH)the National Eye Institute of the National Institutes of Health under Award Number P30EY029220(to MSH)。
文摘Vision restoration presents a considerable challenge in the realm of regenerative medicine,while recent progress in ultrasound stimulation has displayed potential as a non-invasive therapeutic approach.This narrative review offers a comprehensive overview of current research on ultrasound-stimulated neuromodulation,emphasizing its potential as a treatment modality for various nerve injuries.By examining of the efficacy of different types of ultrasound stimulation in modulating peripheral and optic nerves,we can delve into their underlying molecular mechanisms.Furthermore,the review underscores the potential of sonogenetics in vision restoration,which involves leveraging pharmacological and genetic manipulations to inhibit or enhance the expression of related mechanosensitive channels,thereby modulating the strength of the ultrasound response.We also address how methods such as viral transcription can be utilized to render specific neurons or organs highly responsive to ultrasound,leading to significantly improved therapeutic outcomes.
文摘Parkinson’s disease is a complex,progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra,leading to motor and non-motor symptoms.While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief,they do not halt disease progression.In recent years,significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease,including alpha-synuclein aggregation,mitochondrial dysfunction,neuroinflammation,and lysosomal impairment.These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression.This review comprehensively explores emerging approaches such as gene and cell therapies,LRRK2 inhibitors,alpha-synuclein immunotherapy,and gut microbiota modulation.We also discuss the therapeutic potential of mitophagy activators,digital biomarkers,and neuromodulation techniques.Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms.Special attention is given to recent clinical trials(2023–2025),translational gaps,and the potential of personalized medicine in Parkinson’s disease management.Furthermore,we examine the integration of multi-omics data and digital tools in advancing precision therapeutics.Overall,this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.
文摘BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder,with limited evidence for pharmacotherapy.Treatment typically involves medication,cognitive behavioral therapy,and behavioral interventions.Recently,transcranial magnetic stimulation(TMS)has emerged as a potential treatment strategy.AIM To assess the role of TMS in treating trichotillomania.METHODS A systematic search using specific terms was done in PubMed and Scopus databases for articles published until May 17,2024,related to trichotillomania and TMS.The search included randomized controlled trials,open-label studies,case series,case reports,and retrospective chart reviews,following the Preferred Items for Systematic Reviews and Meta-Analysis guideline.RESULTS We identified 32 articles(6 in PubMed and 26 in Scopus).After removing duplicates and articles that did not meet the selection criteria,we conducted a final analysis of four articles.These included one retrospective study,two case series,and one case study,with a total of 22 patients diagnosed with trichotillomania enrolled across all four studies.The brain areas targeted were the supplementary motor area(SMA),pre-SMA,and left dorsolateral prefrontal cortex.The studies reported an improvement in the severity of symptoms of trichotillomania in the majority of patients with negligible side effects.Nevertheless,it is important to note that the existing studies are mostly of low to moderate quality.CONCLUSION Early evidence suggests repetitive TMS and accelerated continuous theta burst stimulation can help treat trichotillomania adjunctively to other treatments.
文摘Parkinson’s disease patients,in addition to typical motor symptoms,often experience various psychological symptoms,including depression,anxiety,cognitive impairment,impulse control disorders,and psychotic symptoms.These symptoms severely affect patients’quality of life and may even cause a greater disease burden than motor symptoms.This review focuses on the application progress of transcranial magnetic stimulation(TMS)as a non-invasive neuromodulation technique in the treatment of psychological symptoms in Parkinson’s disease.Studies have shown that repetitive TMS(rTMS)has significant improvement effects on Parkinson’s disease-related depressive symptoms,with mechanisms possibly related to the regulation of the prefrontal-striatal dopamine pathway and the promotion of neuroplasticity.For anxiety symptoms,continuous theta burst stimulation has shown potential in indirect regulation of the amygdala and hippocampal regions.For cognitive impairment,high-frequency rTMS applied to the dorsolateral prefrontal cortex can improve executive function deficits,while bilateral coordinated stimulation protocols help enhance attention and memory functions.For impulse control disorders in Parkinson’s disease patients,inhibitory stimulation applied to the orbitofrontal cortex can alleviate pathological gambling and compulsive behaviors.In terms of sleep disorders,TMS has also shown potential efficacy in regulating circadian rhythms and improving rapid eye movement sleep behavior disorder.However,current research still has limitations such as small sample sizes,non-standardized stimulation protocols,and insufficient evaluation of long-term efficacy.Future research directions should focus on optimizing stimulation parameters,exploring individualized treatment protocols,integrating multimodal imaging assessments,and conducting large-sample randomized controlled trials to clarify the clinical application value of TMS in the rehabilitation of psychological symptoms in Parkinson’s disease,providing new approaches for the comprehensive management of this common neurodegenerative disease.
基金supported by the Key Collaborative Research Program of the Alliance of International Science Organizations(ANSO-CR-KP-2022-10)Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0200200)+2 种基金Natural Science Foundation of China(82151307,82202253,and 31620103905)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030207)Science Frontier Program of the Chinese Academy of Sciences(QYZDJ-SSW-SMCO19).
文摘Closed-loop neuromodulation,especially using the phase of the electroencephalography(EEG)rhythm to assess the real-time brain state and optimize the brain stimulation process,is becoming a hot research topic.Because the EEG signal is non-stationary,the commonly used EEG phase-based prediction methods have large variances,which may reduce the accuracy of the phase prediction.In this study,we proposed a machine learning-based EEG phase prediction network,which we call EEG phase prediction network(EPN),to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data.We verified the performance of EPN on pre-recorded data,simulated EEG data,and a real-time experiment.Compared with widely used state-of-the-art models(optimized multi-layer filter architecture,auto-regress,and educated temporal prediction),EPN achieved the lowest variance and the greatest accuracy.Thus,the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
