Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests suc...The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.展开更多
Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord ...Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.展开更多
Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are...Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.展开更多
The arc-linear motor(ALM) is a new type of special motor derived from the linear motor, which has the merits of high torque, compact structure and fast dynamic response. This kind of motor does not need a complex inte...The arc-linear motor(ALM) is a new type of special motor derived from the linear motor, which has the merits of high torque, compact structure and fast dynamic response. This kind of motor does not need a complex intermediate transmission device, it is used in some direct-drive applications for continuous rotation or limited angle motion. However, there is no systematic summary and generalization of the ALMs so far.Therefore, this paper systematically overviews the recent advances in ALMs for direct-drive systems. First, the evolution process and basic structure of the ALM are introduced. And then, various ALMs are reviewed with particular reference to motor topologies, working principle, motor performance,optimization design and control techniques. To heel, a comprehensive comparison of several typical ALMs is carried out. Finally, the application areas, main challenges and development trends of the ALMs are highlighted.展开更多
Dear Editor,The primary motor cortex,also known as MOp in rodents,F1,or M1 in primates[1],plays a crucial role in autonomous motor control.It is interconnected with other motor control structures such as the basal gan...Dear Editor,The primary motor cortex,also known as MOp in rodents,F1,or M1 in primates[1],plays a crucial role in autonomous motor control.It is interconnected with other motor control structures such as the basal ganglia,thalamus,and brainstem.Among these connections,the corticostriatal system plays a significant role in functions including action selection,motor control,sequence learning,and habit formation[2].展开更多
Switched Reluctance Motors(SRMs),outfitted with rugged construction,good speed range,high torque density,and rare earth-free nature that outweigh induction motors(IM)and permanent magnet synchronous motor(PMSM),afford...Switched Reluctance Motors(SRMs),outfitted with rugged construction,good speed range,high torque density,and rare earth-free nature that outweigh induction motors(IM)and permanent magnet synchronous motor(PMSM),afford a broad range of applications in the domain of electric vehicles(EVs).Standard copper magnetic wire and low-carbon steel laminations are used to construct SRMs,which give them high efficiency in the range of 85-95%.Despite SRM's desirable features over traditional motor-speed drives,high torque ripples and radial distortions constrain their deployment in EVs.Precise rotor position is imperative for effective management of the speed and torque of SRMs.This paper provides an illustrative compendium on review of the torque-speed control and ripple mitigation techniques using design enhancements and control methods for SRM drives for EV applications.The various schemes were evaluated on their performance metricsoperational speed range,control complexity,practical realization,need for pre-stored parameters(look-up tables of current,inductance and torque profiles)and motor controller memory requirements.The findings provide valuable insights into balancing the gains and trade-offs associated with EV applications.Furthermore,they pinpoint opportunities for enhancement by analyzing the cost and technical aspects of different SRM controllers.展开更多
The hyperloop idea,which is one of the most ecofriendly,low-carbon emissions,and fossil fuel-efficient modes of transportation,has recently become quite popular.In this study,a double-sided linear induction motor(LIM)...The hyperloop idea,which is one of the most ecofriendly,low-carbon emissions,and fossil fuel-efficient modes of transportation,has recently become quite popular.In this study,a double-sided linear induction motor(LIM)with 500 W of output power,60 N of thrust force and 200 V/38.58 Hz of supply voltage was designed to be used in hyperloop development competition hosted by the scientific and technological research council of turkey(TüB?TAK)rail transportation technologies institute(RUTE).In contrast to the studies in the literature,concentrated winding is preferred instead of distributed winding due to mechanical constraints.The electromagnetic design of LIM,whose mechanical and electrical requirements were determined considering the hyperloop development competition,was carried out by following certain steps.Then,the designed model was simulated and analyzed by finite element method(FEM),and the necessary optimizations have been performed to improve the motor characteristics.By examining the final model,the applicability of the concentrated winding type LIM for hyperloop technology has been investigated.Besides,the effects of primary material,railway material,and mechanical air-gap length on LIM performance were also investigated.In the practical phase of the study,the designed LIM has been prototyped and tested.The validation of the experimental results was achieved through good agreement with the finite element analysis results.展开更多
Background:Acupuncture is widely used in modulating brain excitability and motor function,as a form of complementary and alternative medicine.However,there is no existing meta-analysis evaluating the effectiveness and...Background:Acupuncture is widely used in modulating brain excitability and motor function,as a form of complementary and alternative medicine.However,there is no existing meta-analysis evaluating the effectiveness and safety of acupuncture on corticospinal excitability(CSE),and the credibility of the evidence has yet to be quantified.Objective:This study was designed to assess the efficacy and safety of electroacupuncture(EA)and manual acupuncture(MA)in enhancing brain excitability,specifically focusing on CSE as measured by transcranial magnetic stimulation(TMS).Search strategy:This study followed a systematic approach,searching 9 databases up to August 2024 and examining grey literature,in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Inclusion criteria:Studies were included if they compared the clinical efficacy of EA or MA with sham acupuncture,no treatment or usual training.Data extraction and analysis:Three investigators independently conducted literature screening,data extraction,and risk of bias assessment.The primary outcome focused on motor-evoked potentials as measured by TMS,with treatment effects quantified using mean differences or standardized mean differences between pre-and post-treatment.Subgroup analyses were conducted using mixed-effects models,while random-effects or fixed-effects models were used to estimate average treatment differences across studies.Results:Based on 34 studies involving 1031 adults,acupuncture techniques significantly enhanced CSE.EA had a greater impact than MA,with effect sizes of 0.53 mV vs 0.43 mV(95%confidence interval[CI]:[0.30,0.76],P<0.00001 vs 95%CI:[0.28,0.59],P<0.00001).The 5 most frequently used acupoints were LI4(Hegu,32 times),ST36(Zusanli,10 times),LI11(Quchi,7 times),TE5(Waiguan,6 times),and GB34(Yanglingquan,5 times).Conclusion:This systematic review indicates that both EA and MA could effectively and safely enhance CSE,bringing the corticospinal pathway closer to the threshold for firing,which may ultimately improve motor function.LI4,ST36,LI11,TE5 and GB34 are the most commonly used acupoints.展开更多
Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believ...Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.展开更多
Reach-to-grasp movements require integrating information on both object location and grip type,but how these elements are planned and to what extent they interact remains unclear.We designed a new experimental paradig...Reach-to-grasp movements require integrating information on both object location and grip type,but how these elements are planned and to what extent they interact remains unclear.We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays,requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures.Neural activity in the dorsal premotor cortex(PMd)revealed that reach and grasp were similarly represented yet not independent.Upon receiving the second cue,the PMd continued encoding the first,but over half of the neurons displayed incongruent modulations:enhanced,attenuated,or even reversed.Population-level analysis showed significant changes in encoding structure,forming distinct neural patterns.Leveraging canonical correlation analysis,we identified a shared subspace preserving the initial cue’s encoding,contributed by both congruent and incongruent neurons.Together,these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd,providing insights into potential applications for brain–machine interfaces.展开更多
Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons,and high-frequency repetitive transcranial magnetic stimulation can increase the exc...Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons,and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons.However,there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction.We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function.This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction.These patients were randomly assigned to three groups.The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex(M1).The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1.Finally,the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1.A total of 135 seconds of stimulation was applied in the sham group and high-frequency group.At 2 weeks after treatment,cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment.Moreover,motor function scores were significantly improved.The above indices for the low-and high-frequency groups were significantly different compared with the sham group.However,there was no significant difference between the low-and high-frequency groups.The results show that low-and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.展开更多
Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery ...Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.展开更多
A new type of brushless DC motor has been developed by using a square wave rare earth permanent magnet synchronous motor with its double loop control circuit. The double loop control scheme of the drive system yie...A new type of brushless DC motor has been developed by using a square wave rare earth permanent magnet synchronous motor with its double loop control circuit. The double loop control scheme of the drive system yields a combination of desired characteristics including simplified control structure, small ripple torque, high speed accuracy, wide operating speed range, and fast dynamic response. Experimental results confirm excellent characteristics of the motor.展开更多
By imitating the behavioral characteristics of some typical animals, researchers develop bionic stepping motors to extend the working range of piezoelectric materials and utilize their high accuracy advantage as well....By imitating the behavioral characteristics of some typical animals, researchers develop bionic stepping motors to extend the working range of piezoelectric materials and utilize their high accuracy advantage as well. A comprehensive review of the bionic stepping motors driven by piezoelectric materials is presented in this work. The main parts of stepping piezoelectric motors, including the feeding module, clamping module, and other critical components, are introduced elaborately. We classify the bionic stepping piezoelectric motors into inchworm motors, seal motors, and inertia motors depending on their main structure modules, and present the mutual transformation relationships among the three types. In terms of the relative position relationships among the main structure modules, each of the inchworm motors, seal motors, and inertia motors can further be divided into walker type, pusher type, and hybrid type. The configurations and working principles of all bionic stepping piezoelectric motors are reported, followed by a discussion of the advantages and disadvantages of the performance for each type. This work provides theoretical support and thoughtful insights for the understanding, analysis, design, and application of the bionic stepping piezoelectric motors.展开更多
Model predictive control(MPC)has been deemed as an attractive control method in motor drives by virtue of its simple structure,convenient multi-objective optimization,and satisfactory dynamic performance.However,the s...Model predictive control(MPC)has been deemed as an attractive control method in motor drives by virtue of its simple structure,convenient multi-objective optimization,and satisfactory dynamic performance.However,the strong reliance on mathematical models seriously restrains its practical application.Therefore,improving the robustness of MPC has attained significant attentions in the last two decades,followed by which,model-free predictive control(MFPC)comes into existence.This article aims to reveal the current state of MFPC strategies for motor drives and give the categorization from the perspective of implementation.Based on this review,the principles of the reported MFPC strategies are introduced in detail,as well as the challenges encountered in technology realization.In addition,some of typical and important concepts are experimentally validated via case studies to evaluate the performance and highlight their features.Finally,the future trends of MFPC are discussed based on the current state and reported developments.展开更多
Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modula...Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified.This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper(SMAp)in modulating MSL across different complexity levels and for both hands,as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation.Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL,which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions,particularly in interhemispheric connections.These findings may have important clinical implications,particularly for motor rehabilitation in populations such as post-stroke patients.展开更多
Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
This article presents a novel electrical/mechanical hybrid 4-redundancy brushless DC torque motor （BLDCM）, which has found applications in direct drive actuators （DDA） of aerial vehicles. This motor is characteris...This article presents a novel electrical/mechanical hybrid 4-redundancy brushless DC torque motor （BLDCM）, which has found applications in direct drive actuators （DDA） of aerial vehicles. This motor is characteristic of electrical/mechanical hybrid 4-redundancy by securing two stators along with two rotors on the same shaft. Each stator contains two sets of windings embed- ded in separated slots. Furthermore, compared to the scheme of two electrical dual-redundancy BLDCMs linked by a mechanical transmission, the proposed motor has lower volume and lighter weight, eliminates the nonlinearity caused by the gap of the me- chanical transmission, moderates the requirement for the torque balance between redundancies and reduces the cogging torque by shifting the magnets. Both magnetic circuit calculation and the finite element analysis （FEA） of the electromagnetic field are conducted to optimize the design process. A prototype motor has been produced and tested. The results indicate that its perform- ances comply with the requirements presented by designers. Moreover, the position frequency response of the prototype in the DDA＇s unloaded situation has also demonstrated the fulfillment of desired dynamic characteristics.展开更多
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
文摘The increasing global prevalence of mild cognitive impairment(MCI)necessitates a paradigm shift in early detection strategies.Conventional neuropsychological assessment methods,predominantly paper-and-pencil tests such as the Mini-Mental State Examination and the Montreal Cognitive Assessment,exhibit inherent limitations with respect to accessibility,administration burden,and sensitivity to subtle cognitive decline,particularly among diverse populations.This commentary critically examines a recent study that champions a novel approach:The integration of gait and handwriting kinematic parameters analyzed via machine learning for MCI screening.The present study positions itself within the broader landscape of MCI detection,with a view to comparing its advantages against established neuropsychological batteries,advanced neuroimaging(e.g.,positron emission tomography,magnetic resonance imaging),and emerging fluid biomarkers(e.g.,cerebrospinal fluid,blood-based assays).While the study demonstrates promising accuracy(74.44%area under the curve 0.74 with gait and graphic handwriting)and addresses key unmet needs in accessibility and objectivity,we highlight its cross-sectional nature,limited sample diversity,and lack of dual-task assessment as areas for future refinement.This commentary posits that kinematic biomarkers offer a distinctive,scalable,and ecologically valid approach to widespread MCI screening,thereby complementing existing methods by providing real-world functional insights.Future research should prioritize longitudinal validation,expansion to diverse cohorts,integration with multimodal data including dual-tasking,and the development of highly portable,artificial intelligence-driven solutions to achieve the democratization of early MCI detection and enable timely interventions.
基金supported by a grant from Ministry of Science and Technology China,No.2022ZD0204704(to WW)the National Natural Science Foundation of China,No.82301572(to XZ)the China Postdoctoral Science Foundation,No.2023M731202(to XZ)。
文摘Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.
基金supported by Craig H.Neilsen Foundation,Wings for Life Foundation,Canadian Institutes of Health Research,and Fonds de Recherche Québec-Santé(to FB).
文摘Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.
基金supported in part by the National Natural Science Foundation of China under Grants 52307049 and U23A20644in part by the Fundamental Research Funds for the Central Universities under Grant JZ2023HGTB0243+1 种基金in part by the Key Laboratory of Electric Drive and Control of Anhui Province under Grant DQKJ202403in part by the China Postdoctoral Science Foundation under Grant 2024M751073。
文摘The arc-linear motor(ALM) is a new type of special motor derived from the linear motor, which has the merits of high torque, compact structure and fast dynamic response. This kind of motor does not need a complex intermediate transmission device, it is used in some direct-drive applications for continuous rotation or limited angle motion. However, there is no systematic summary and generalization of the ALMs so far.Therefore, this paper systematically overviews the recent advances in ALMs for direct-drive systems. First, the evolution process and basic structure of the ALM are introduced. And then, various ALMs are reviewed with particular reference to motor topologies, working principle, motor performance,optimization design and control techniques. To heel, a comprehensive comparison of several typical ALMs is carried out. Finally, the application areas, main challenges and development trends of the ALMs are highlighted.
基金supported by the National Key R&D Program of China(2020YFE0205900 and 2022YEF0203200)the STI 2030-Major Project(2021ZD0200104 and 2022ZD0205203)+2 种基金the Shenzhen Science and Technology Program(RCYX20210706092100003,RCBS20221008093311027,and JCYJ20210324102006018)the Youth Innovation Promotion Association CAS(2022367)the Shenzhen Technological Research Center for Primate Translational Medicine grant(XMHT20220104005).
文摘Dear Editor,The primary motor cortex,also known as MOp in rodents,F1,or M1 in primates[1],plays a crucial role in autonomous motor control.It is interconnected with other motor control structures such as the basal ganglia,thalamus,and brainstem.Among these connections,the corticostriatal system plays a significant role in functions including action selection,motor control,sequence learning,and habit formation[2].
基金supported in part by the Universitat Politècnica de València under grant PAID-10-21supported through AMRITA Seed Grant(Proposal ID:ASG2022188)。
文摘Switched Reluctance Motors(SRMs),outfitted with rugged construction,good speed range,high torque density,and rare earth-free nature that outweigh induction motors(IM)and permanent magnet synchronous motor(PMSM),afford a broad range of applications in the domain of electric vehicles(EVs).Standard copper magnetic wire and low-carbon steel laminations are used to construct SRMs,which give them high efficiency in the range of 85-95%.Despite SRM's desirable features over traditional motor-speed drives,high torque ripples and radial distortions constrain their deployment in EVs.Precise rotor position is imperative for effective management of the speed and torque of SRMs.This paper provides an illustrative compendium on review of the torque-speed control and ripple mitigation techniques using design enhancements and control methods for SRM drives for EV applications.The various schemes were evaluated on their performance metricsoperational speed range,control complexity,practical realization,need for pre-stored parameters(look-up tables of current,inductance and torque profiles)and motor controller memory requirements.The findings provide valuable insights into balancing the gains and trade-offs associated with EV applications.Furthermore,they pinpoint opportunities for enhancement by analyzing the cost and technical aspects of different SRM controllers.
基金the Istanbul Technical University Scientific Research Projects Unit with grant number MGA-2022-43948。
文摘The hyperloop idea,which is one of the most ecofriendly,low-carbon emissions,and fossil fuel-efficient modes of transportation,has recently become quite popular.In this study,a double-sided linear induction motor(LIM)with 500 W of output power,60 N of thrust force and 200 V/38.58 Hz of supply voltage was designed to be used in hyperloop development competition hosted by the scientific and technological research council of turkey(TüB?TAK)rail transportation technologies institute(RUTE).In contrast to the studies in the literature,concentrated winding is preferred instead of distributed winding due to mechanical constraints.The electromagnetic design of LIM,whose mechanical and electrical requirements were determined considering the hyperloop development competition,was carried out by following certain steps.Then,the designed model was simulated and analyzed by finite element method(FEM),and the necessary optimizations have been performed to improve the motor characteristics.By examining the final model,the applicability of the concentrated winding type LIM for hyperloop technology has been investigated.Besides,the effects of primary material,railway material,and mechanical air-gap length on LIM performance were also investigated.In the practical phase of the study,the designed LIM has been prototyped and tested.The validation of the experimental results was achieved through good agreement with the finite element analysis results.
文摘Background:Acupuncture is widely used in modulating brain excitability and motor function,as a form of complementary and alternative medicine.However,there is no existing meta-analysis evaluating the effectiveness and safety of acupuncture on corticospinal excitability(CSE),and the credibility of the evidence has yet to be quantified.Objective:This study was designed to assess the efficacy and safety of electroacupuncture(EA)and manual acupuncture(MA)in enhancing brain excitability,specifically focusing on CSE as measured by transcranial magnetic stimulation(TMS).Search strategy:This study followed a systematic approach,searching 9 databases up to August 2024 and examining grey literature,in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Inclusion criteria:Studies were included if they compared the clinical efficacy of EA or MA with sham acupuncture,no treatment or usual training.Data extraction and analysis:Three investigators independently conducted literature screening,data extraction,and risk of bias assessment.The primary outcome focused on motor-evoked potentials as measured by TMS,with treatment effects quantified using mean differences or standardized mean differences between pre-and post-treatment.Subgroup analyses were conducted using mixed-effects models,while random-effects or fixed-effects models were used to estimate average treatment differences across studies.Results:Based on 34 studies involving 1031 adults,acupuncture techniques significantly enhanced CSE.EA had a greater impact than MA,with effect sizes of 0.53 mV vs 0.43 mV(95%confidence interval[CI]:[0.30,0.76],P<0.00001 vs 95%CI:[0.28,0.59],P<0.00001).The 5 most frequently used acupoints were LI4(Hegu,32 times),ST36(Zusanli,10 times),LI11(Quchi,7 times),TE5(Waiguan,6 times),and GB34(Yanglingquan,5 times).Conclusion:This systematic review indicates that both EA and MA could effectively and safely enhance CSE,bringing the corticospinal pathway closer to the threshold for firing,which may ultimately improve motor function.LI4,ST36,LI11,TE5 and GB34 are the most commonly used acupoints.
基金supported by the Key Project at the Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)the National Natural Science Foundation of China(No.82104389)+2 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2023E002)the High-level Key Discipline Program of National Administration of Traditional Chinese Medicine(No.ZYYZDXK-2023244)China Agricultural Research System of MOF and MARA(No.CARS-21).
文摘Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.
基金supported by STI 2030-Major Projects(2022ZD0208903)the National Natural Science Foundation of China(62336007)+3 种基金the Natural Science Foundation of Shandong Province(ZR2024QH582)the Pioneer R&D Program of Zhejiang Province(2024C03001)the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-002)the Fundamental Research Funds for the Central Universities(2024ZFJH01-01).
文摘Reach-to-grasp movements require integrating information on both object location and grip type,but how these elements are planned and to what extent they interact remains unclear.We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays,requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures.Neural activity in the dorsal premotor cortex(PMd)revealed that reach and grasp were similarly represented yet not independent.Upon receiving the second cue,the PMd continued encoding the first,but over half of the neurons displayed incongruent modulations:enhanced,attenuated,or even reversed.Population-level analysis showed significant changes in encoding structure,forming distinct neural patterns.Leveraging canonical correlation analysis,we identified a shared subspace preserving the initial cue’s encoding,contributed by both congruent and incongruent neurons.Together,these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd,providing insights into potential applications for brain–machine interfaces.
基金several colleague therapists of the Rehabilitation Medicine Department of the Affiliated Hospital of Qingdao University of China for their support and selfless help
文摘Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons,and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons.However,there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction.We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function.This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction.These patients were randomly assigned to three groups.The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex(M1).The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1.Finally,the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1.A total of 135 seconds of stimulation was applied in the sham group and high-frequency group.At 2 weeks after treatment,cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment.Moreover,motor function scores were significantly improved.The above indices for the low-and high-frequency groups were significantly different compared with the sham group.However,there was no significant difference between the low-and high-frequency groups.The results show that low-and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.
基金supported by the NIH (R01NS103481, R01NS111776, and R01NS131489)Indiana Department of Health (ISDH58180)(all to WW)。
文摘Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.
文摘A new type of brushless DC motor has been developed by using a square wave rare earth permanent magnet synchronous motor with its double loop control circuit. The double loop control scheme of the drive system yields a combination of desired characteristics including simplified control structure, small ripple torque, high speed accuracy, wide operating speed range, and fast dynamic response. Experimental results confirm excellent characteristics of the motor.
基金Natural Science Foundation of Jilin Province,20220101216JC,Shupeng WangTalent Introduction Fund of Jilin University,451210330007,Shupeng Wang.
文摘By imitating the behavioral characteristics of some typical animals, researchers develop bionic stepping motors to extend the working range of piezoelectric materials and utilize their high accuracy advantage as well. A comprehensive review of the bionic stepping motors driven by piezoelectric materials is presented in this work. The main parts of stepping piezoelectric motors, including the feeding module, clamping module, and other critical components, are introduced elaborately. We classify the bionic stepping piezoelectric motors into inchworm motors, seal motors, and inertia motors depending on their main structure modules, and present the mutual transformation relationships among the three types. In terms of the relative position relationships among the main structure modules, each of the inchworm motors, seal motors, and inertia motors can further be divided into walker type, pusher type, and hybrid type. The configurations and working principles of all bionic stepping piezoelectric motors are reported, followed by a discussion of the advantages and disadvantages of the performance for each type. This work provides theoretical support and thoughtful insights for the understanding, analysis, design, and application of the bionic stepping piezoelectric motors.
基金supported in part by the National Natural Science Foundation of China under Grant 52077002。
文摘Model predictive control(MPC)has been deemed as an attractive control method in motor drives by virtue of its simple structure,convenient multi-objective optimization,and satisfactory dynamic performance.However,the strong reliance on mathematical models seriously restrains its practical application.Therefore,improving the robustness of MPC has attained significant attentions in the last two decades,followed by which,model-free predictive control(MFPC)comes into existence.This article aims to reveal the current state of MFPC strategies for motor drives and give the categorization from the perspective of implementation.Based on this review,the principles of the reported MFPC strategies are introduced in detail,as well as the challenges encountered in technology realization.In addition,some of typical and important concepts are experimentally validated via case studies to evaluate the performance and highlight their features.Finally,the future trends of MFPC are discussed based on the current state and reported developments.
基金supported by grants from the Zhejiang Provincial Natural Science Foundation(LGJ22H180001)Zhejiang Medical and Health Science and Technology Project(2021KY249)the National Key R&D Program of China(2017YFC1310000).
文摘Attempts have been made to modulate motor sequence learning(MSL)through repetitive transcranial magnetic stimulation,targeting different sites within the sensorimotor network.However,the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified.This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper(SMAp)in modulating MSL across different complexity levels and for both hands,as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation.Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL,which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions,particularly in interhemispheric connections.These findings may have important clinical implications,particularly for motor rehabilitation in populations such as post-stroke patients.
基金supported by the National Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
基金New Century Program For Excellent Talents of Ministry of Education of China (NCET-04-0163)
文摘This article presents a novel electrical/mechanical hybrid 4-redundancy brushless DC torque motor （BLDCM）, which has found applications in direct drive actuators （DDA） of aerial vehicles. This motor is characteristic of electrical/mechanical hybrid 4-redundancy by securing two stators along with two rotors on the same shaft. Each stator contains two sets of windings embed- ded in separated slots. Furthermore, compared to the scheme of two electrical dual-redundancy BLDCMs linked by a mechanical transmission, the proposed motor has lower volume and lighter weight, eliminates the nonlinearity caused by the gap of the me- chanical transmission, moderates the requirement for the torque balance between redundancies and reduces the cogging torque by shifting the magnets. Both magnetic circuit calculation and the finite element analysis （FEA） of the electromagnetic field are conducted to optimize the design process. A prototype motor has been produced and tested. The results indicate that its perform- ances comply with the requirements presented by designers. Moreover, the position frequency response of the prototype in the DDA＇s unloaded situation has also demonstrated the fulfillment of desired dynamic characteristics.
