Purpose:Ankle proprioception deficits have been widely reported in patients with chronic ankle instability(CAI),but their central neuropathological mechanisms have not been fully discussed.So,we aimed to figure out wh...Purpose:Ankle proprioception deficits have been widely reported in patients with chronic ankle instability(CAI),but their central neuropathological mechanisms have not been fully discussed.So,we aimed to figure out whether the structural and functional features of the cerebellar vermis differed between patients with CAI and healthy controls,and are associated with proprioception deficits in patients.Methods:Twenty-two patients and 25 control individuals were enrolled in a cross-sectional investigation.All participants underwent structural and resting-state functional magnetic resonance imaging scanning to calculate voxel-based morphometry(VBM)and fractional amplitude of low-frequency fluctuation(fALFF)of the vermis.Between-group comparisons of the ankle instability-related subregions of the vermis were performed.Correlation analyses were performed between the outcomes of the surviving subregions and the proprioceptive scores of the ankle inversion discrimination apparatus for landing test.Results:The subregion of vermis Ⅳ/Ⅴ survived the multiple comparison correction to reveal a lower VBM value in patients than in healthy controls(Cohen's d=-0.968).The patients also showed significantly higher fALFF(Cohen's d=0.666)in this subregion.After controlling the demographic features,the proprioceptive scores were significantly correlated with VBM(r=0.622)and fALFF values(r=-0.512)in the group of patients.Conclusions:Patients with CAI have lower gray matter volume and higher activity intensity in the cerebellar vermis than healthy control.The more severe proprioception deficits were significantly associated with the vermal volume and activity,which might be able to facilitate future diagnoses and treatments for CAI.展开更多
Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage se...Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.展开更多
Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network lev...Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.展开更多
Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association ...Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.Methods:UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted.Then,the two-sample Mendelian randomization(MR)analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship.Finally,genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.Results:Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates(odd ratio[OR]ranged from 1.632 to 1.658).Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls(OR=1.036)and a lower fractional anisotropy of superior cerebellar peduncle(SCP)(left,β=0.052;right,β=0.053).A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls(β=0.003).Conclusion:The history of ankle-foot sprains is associated with a slightly increased risk of falls.These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries.展开更多
Purpose Lateral ankle sprains(LAS)are associated with corticospinal pathway deficits.Existing evidence is primarily based on cross-sectional investigations and noncausal speculations.This study aims to determine wheth...Purpose Lateral ankle sprains(LAS)are associated with corticospinal pathway deficits.Existing evidence is primarily based on cross-sectional investigations and noncausal speculations.This study aims to determine whether maladaptive corticospinal pathway alterations occur pre-and postligament transection in LAS mouse models.Additionally,this study explores whether the alterations are more pronounced in adolescent mice than adults.Methods Twenty-four 8-week-old adolescent and twenty-four 24-week-old adult mice were randomly assigned to lateral ankle ligament transection or sham surgery.Diffusion-weighted imaging of the corticospinal pathway was performed presurgery and 8 weeks postsurgery.Fractional anisotropy(FA)values,reflecting fiber integrity within the corticospinal subregions of the medulla,pons,midbrain,and cerebrum,were extracted.Results Overall,41 mice completed repeated image acquisition.Before surgery,no significant group effects on FA within the four corticospinal subregions were detected in either adolescent or adult mice.Two months after surgery,the adolescent cohort displayed a significant reduction in FA in the medulla subregion following ankle ligament transection(β-baseline-adjusted=-0.083,95%CI,-0.145 to-0.021,p-corrected=0.048).Conversely,no significant effects of ankle ligament transection on corticospinal FA were observed in the adult cohort.Conclusion The maladaptive alterations in the corticospinal tract could be observed in the adolescent LAS mouse model,characterized by reduced fiber integrity in the medulla subregion.While these results are derived from an animal model,they provide a foundation for future investigations into the mechanisms underlying neurological deficits following musculoskeletal injuries.展开更多
Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connect...Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].展开更多
Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potentia...Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.展开更多
To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial mag...To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial magnetic stimulation(rTMS),one of the most commonly applied non-invasive neurostimulation techniques,has shown efficacy in treating neuropsychiatric disorders,such as depression.展开更多
Over the last decade virtual reality （VR） setups for rodents have been developed and utilized to in-vestigate the neural foundations of behavior. Such VR systems became very popular since theyallow the use of state-...Over the last decade virtual reality （VR） setups for rodents have been developed and utilized to in-vestigate the neural foundations of behavior. Such VR systems became very popular since theyallow the use of state-of-the-art techniques to measure neural activity in behaving rodents that can-not be easily used with classical behavior setups. Here, we provide an overview of rodent VR tech-nologies and review recent results from related research. We discuss commonalities and differ-ences as well as merits and issues of different approaches. A special focus is given to experimental（behavioral） paradigms in use. Finally we comment on possible use cases that may further exploitthe potential of VR in rodent research and hence inspire future studies.展开更多
As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterio...As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.展开更多
Chinese,as a logographic language,fundamentally differs from alphabetic languages like English.Previous neuroimaging studies have mainly focused on alphabetic languages,while the exploration of Chinese reading is stil...Chinese,as a logographic language,fundamentally differs from alphabetic languages like English.Previous neuroimaging studies have mainly focused on alphabetic languages,while the exploration of Chinese reading is still an emerging and fast-growing research field.Recently,a growing number of neuroimaging studies have explored the neural circuit of Chinese reading.Here,we summarize previous research on Chinese reading from a connectomic perspective.Converging evidence indicates that the left middle frontal gyrus is a specialized hub region that connects the ventral with dorsal pathways for Chinese reading.Notably,the orthography-to-phonology and orthography-to-semantics mapping,mainly processed in the ventral pathway,are more specific during Chinese reading.Besides,in addition to the left-lateralized language-related regions,reading pathways in the right hemisphere also play an important role in Chinese reading.Throughout,we comprehensively review prior findings and emphasize several challenging issues to be explored in future work.展开更多
It has been almost 50 years since the term“brain–computer interface”(BCI)was first proposed by Jacques J.Vidal in 1973[1].Unlike traditional electronic interfaces that transmit nonliving information between devices...It has been almost 50 years since the term“brain–computer interface”(BCI)was first proposed by Jacques J.Vidal in 1973[1].Unlike traditional electronic interfaces that transmit nonliving information between devices,BCIs set up a communication bridge between a living brain and nonliving devices.Technically speaking,a BCI is a system that measures brain activity and converts it into the artificial outputs that replace,restore,enhance,supplement,or improve the natural central nervous system outputs[2].At present,electroencephalography(EEG)is the most commonly used brain signal for BCIs.展开更多
Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence...Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders.An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive.Consequently,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often ineffective.This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis.Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected cases.In this review,we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis.In addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.展开更多
Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produ...Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produced.In some scienti fic studies,it is necessary to dissect the axons and dendrites,which is typically done manually and is both tedious and time-consuming.To automate this process,we have developed a method that relies solely on neuronal skeletons using Geometric Deep Learning(GDL).We demonstrate the effectiveness of this method using pyramidal neurons in mammalian brains,and the results are promising for its application in neuroscience studies.展开更多
The brain function of prediction is fundamental for human beings to shape perceptions efficiently and successively. Through decades of effort, a valuable brain activation map has been obtained for prediction. However,...The brain function of prediction is fundamental for human beings to shape perceptions efficiently and successively. Through decades of effort, a valuable brain activation map has been obtained for prediction. However,much less is known about how the brain manages the prediction process over time using traditional neuropsychological paradigms. Here, we implemented an innovative paradigm for timing prediction to precisely study the temporal dynamics of neural oscillations. In the experiment recruiting 45 participants, expectation suppression was found for the overall electroencephalographic activity,consistent with previous hemodynamic studies. Notably,we found that N1 was positively associated with predictability while N2 showed a reversed relation to predictability. Furthermore, the matching prediction had a similar profile with no timing prediction, both showing an almost saturated N1 and an absence of N2. The results indicate that the N1 process showed a ‘sharpening' effect for predictable inputs, while the N2 process showed a‘dampening' effect. Therefore, these two paradoxical neural effects of prediction, which have provoked wide confusion in accounting for expectation suppression,actually co-exist in the procedure of timing prediction but work in separate time windows. These findings strongly support a recently-proposed opposing process theory.展开更多
Detecting moving objects in the stationary background is an important problem in visual surveillance systems.However,the traditional background subtraction method fails when the background is not completely stationary...Detecting moving objects in the stationary background is an important problem in visual surveillance systems.However,the traditional background subtraction method fails when the background is not completely stationary and involves certain dynamic changes.In this paper,according to the basic steps of the background subtraction method,a novel non-parametric moving object detection method is proposed based on an improved ant colony algorithm by using the Markov random field.Concretely,the contributions are as follows:1)A new nonparametric strategy is utilized to model the background,based on an improved kernel density estimation;this approach uses an adaptive bandwidth,and the fused features combine the colours,gradients and positions.2)A Markov random field method based on this adaptive background model via the constraint of the spatial context is proposed to extract objects.3)The posterior function is maximized efficiently by using an improved ant colony system algorithm.Extensive experiments show that the proposed method demonstrates a better performance than many existing state-of-the-art methods.展开更多
Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks.However,most resting-state functional magnetic resonance imaging(R-fMRI)st...Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks.However,most resting-state functional magnetic resonance imaging(R-fMRI)studies have identified functional hubs by examining spontaneous fluctuations of the blood oxygen level-dependent signal within a typical low-frequency band(e.g.,0.01–0.08 Hz or 0.01–0.1 Hz).Little is known about how the spatial distributions of functional hubs depend on frequency bands of interest.Here,we used repeatedly measured R-fMRI data from 53 healthy young adults and a degree centrality analysis to identify voxelwise frequency-resolved functional hubs and further examined their test-retest reliability across two sessions.We showed that a wide-range frequency band(0.01–0.24 Hz)accessible with a typical sampling rate(fsample=0.5 Hz)could be classified into three frequency bands with distinct patterns,namely,low-frequency(LF,0.01–0.06 Hz),middle-frequency(MF,0.06–0.16 Hz),and high-frequency(HF,0.16–0.24 Hz)bands.The functional hubs were mainly located in the medial and lateral frontal and parietal cortices in the LF band,and in the medial prefrontal cortex,superior temporal gyrus,parahippocampal gyrus,amygdala,and several cerebellar regions in the MF and HF bands.These hub regions exhibited fair to good test-retest reliability,regardless of the frequency band.The presence of the three frequency bands was well replicated using an independent R-fMRI dataset from 45 healthy young adults.Our findings demonstrate reliable frequency-resolved functional connectivity hubs in three categories,thus providing insights into the frequency-specific connectome organization in healthy and disordered brains.展开更多
Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction.However,action recognition currently used in non-human primate(NHP)research ...Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction.However,action recognition currently used in non-human primate(NHP)research relies heavily on intense manual labor and lacks standardized assessment.In this work,we established two standard benchmark datasets of NHPs in the laboratory:Monkeyin Lab(Mi L),which includes 13 categories of actions and postures,and MiL2D,which includes sequences of two-dimensional(2D)skeleton features.Furthermore,based on recent methodological advances in deep learning and skeleton visualization,we introduced the Monkey Monitor Kit(Mon Kit)toolbox for automatic action recognition,posture estimation,and identification of fine motor activity in monkeys.Using the datasets and Mon Kit,we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of Rett syndrome(RTT).Mon Kit was used to assess motor function,stereotyped behaviors,and depressive phenotypes,with the outcomes compared with human manual detection.Mon Kit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency,thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.展开更多
Why Was the Cohort Set Up?Autism spectrum disorder(ASD)is a child neurodevelopmental disorder,the onset of which is generally within 3 years of age,and often leads to lifelong impaired social and cognitive functions,w...Why Was the Cohort Set Up?Autism spectrum disorder(ASD)is a child neurodevelopmental disorder,the onset of which is generally within 3 years of age,and often leads to lifelong impaired social and cognitive functions,which impose significant mental pressure and economic burdens on the family and society.展开更多
基金supported by the National Natural Science Foundation of China[grant numbers 82372492,82072510]National Key R&D Program of China[grant numbers 2018YFC1312900]+1 种基金Shanghai Natural Science Foundation[grant numbers 20ZR1406400]Science and Technology Commission of Shanghai Municipality[grant numbers 22dz1204700].
文摘Purpose:Ankle proprioception deficits have been widely reported in patients with chronic ankle instability(CAI),but their central neuropathological mechanisms have not been fully discussed.So,we aimed to figure out whether the structural and functional features of the cerebellar vermis differed between patients with CAI and healthy controls,and are associated with proprioception deficits in patients.Methods:Twenty-two patients and 25 control individuals were enrolled in a cross-sectional investigation.All participants underwent structural and resting-state functional magnetic resonance imaging scanning to calculate voxel-based morphometry(VBM)and fractional amplitude of low-frequency fluctuation(fALFF)of the vermis.Between-group comparisons of the ankle instability-related subregions of the vermis were performed.Correlation analyses were performed between the outcomes of the surviving subregions and the proprioceptive scores of the ankle inversion discrimination apparatus for landing test.Results:The subregion of vermis Ⅳ/Ⅴ survived the multiple comparison correction to reveal a lower VBM value in patients than in healthy controls(Cohen's d=-0.968).The patients also showed significantly higher fALFF(Cohen's d=0.666)in this subregion.After controlling the demographic features,the proprioceptive scores were significantly correlated with VBM(r=0.622)and fALFF values(r=-0.512)in the group of patients.Conclusions:Patients with CAI have lower gray matter volume and higher activity intensity in the cerebellar vermis than healthy control.The more severe proprioception deficits were significantly associated with the vermal volume and activity,which might be able to facilitate future diagnoses and treatments for CAI.
基金supported by the National Natural Science Foundation of China, No.61932008Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。
文摘Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.
基金supported by the National Natural Science Foundation of China,Nos.81871836(to MZ),82172554(to XH),and 81802249(to XH),81902301(to JW)the National Key R&D Program of China,Nos.2018YFC2001600(to JX)and 2018YFC2001604(to JX)+3 种基金Shanghai Rising Star Program,No.19QA1409000(to MZ)Shanghai Municipal Commission of Health and Family Planning,No.2018YQ02(to MZ)Shanghai Youth Top Talent Development PlanShanghai“Rising Stars of Medical Talent”Youth Development Program,No.RY411.19.01.10(to XH)。
文摘Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.
基金supported by the National Natural Science Foundation of China[No.81871823,81971583,81671652,8207090113]National Key R&D Program of China[No.2018YFC1312900]+3 种基金Natural Science Foundation of Shanghai[No.20ZR1406400]Science and Technology Commission of Shanghai Municipality[No.18JC1410403]Shanghai Municipal Science and Technology Major Project[No.2017SHZDZX01,2018SHZDZX01]Shanghai Science and Technology Committee[No.22dz1204700].
文摘Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.Methods:UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted.Then,the two-sample Mendelian randomization(MR)analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship.Finally,genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.Results:Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates(odd ratio[OR]ranged from 1.632 to 1.658).Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls(OR=1.036)and a lower fractional anisotropy of superior cerebellar peduncle(SCP)(left,β=0.052;right,β=0.053).A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls(β=0.003).Conclusion:The history of ankle-foot sprains is associated with a slightly increased risk of falls.These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries.
基金supported by the National Natural Science Foundation of China[No.81871823,8207090113,82072510]National Key R&D Program of China[No.2018YFC1312900]+2 种基金Shanghai Natural Science Foundation[No.20ZR1406400]Science and Technology Commission of Shanghai Municipality[No.18JC1410403]Shanghai Municipal Science and Technology Major Project[No.2017SHZDZX01,2018SHZDZX01].
文摘Purpose Lateral ankle sprains(LAS)are associated with corticospinal pathway deficits.Existing evidence is primarily based on cross-sectional investigations and noncausal speculations.This study aims to determine whether maladaptive corticospinal pathway alterations occur pre-and postligament transection in LAS mouse models.Additionally,this study explores whether the alterations are more pronounced in adolescent mice than adults.Methods Twenty-four 8-week-old adolescent and twenty-four 24-week-old adult mice were randomly assigned to lateral ankle ligament transection or sham surgery.Diffusion-weighted imaging of the corticospinal pathway was performed presurgery and 8 weeks postsurgery.Fractional anisotropy(FA)values,reflecting fiber integrity within the corticospinal subregions of the medulla,pons,midbrain,and cerebrum,were extracted.Results Overall,41 mice completed repeated image acquisition.Before surgery,no significant group effects on FA within the four corticospinal subregions were detected in either adolescent or adult mice.Two months after surgery,the adolescent cohort displayed a significant reduction in FA in the medulla subregion following ankle ligament transection(β-baseline-adjusted=-0.083,95%CI,-0.145 to-0.021,p-corrected=0.048).Conversely,no significant effects of ankle ligament transection on corticospinal FA were observed in the adult cohort.Conclusion The maladaptive alterations in the corticospinal tract could be observed in the adolescent LAS mouse model,characterized by reduced fiber integrity in the medulla subregion.While these results are derived from an animal model,they provide a foundation for future investigations into the mechanisms underlying neurological deficits following musculoskeletal injuries.
文摘Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].
基金supported by National Natural Science Foundation of China(82374296,82271965,62331021)Development Project of Shanghai Peak Disciplines-Integrated Medicine(201801)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Shanghai Municipal Science and Technology Explorer Project(23TS1400500).
文摘Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.
基金supported by grants from the National Natural Science Foundation of China(82125032,81930095,82204048 and 81761128035)the Science and Technology Commission of Shanghai Municipality(19410713500 and 2018SHZDZX01)+3 种基金the Foundation of Shanghai Municipal Commission of Health and Family Planning(GWV-10.1-XK07,2020CXJQ01 and 2018YJRC03)the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20211100)the Guangdong Key Project(2018B030335001).
文摘To the editor:Social communication impairment(SCI)is a core symptom of autism spectrum disorder(ASD),and evidence-based interventions targeting this domain remain limited.In the past decade,repetitive transcranial magnetic stimulation(rTMS),one of the most commonly applied non-invasive neurostimulation techniques,has shown efficacy in treating neuropsychiatric disorders,such as depression.
文摘Over the last decade virtual reality （VR） setups for rodents have been developed and utilized to in-vestigate the neural foundations of behavior. Such VR systems became very popular since theyallow the use of state-of-the-art techniques to measure neural activity in behaving rodents that can-not be easily used with classical behavior setups. Here, we provide an overview of rodent VR tech-nologies and review recent results from related research. We discuss commonalities and differ-ences as well as merits and issues of different approaches. A special focus is given to experimental（behavioral） paradigms in use. Finally we comment on possible use cases that may further exploitthe potential of VR in rodent research and hence inspire future studies.
基金supported by the National Key R&D Program of China(2019YFA0709504)the National Natural Science Foundation of China(31930042,31771164,31900719,and 91630314)+6 种基金the Innovative Research Team of High-level Local Universities in ShanghaiDevelopment Project of Shanghai Peak Disciplines Integrated Chinese and Western MedicineShanghai Science and Technology Committee Rising-Star Program(19QA1401400)111 Project(B18015)Key Project of Shanghai Science&Technology(16JC1420402)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab。
文摘As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.
基金supported by the Natural Science Foundation of China(81901826 and 61932008)the Natural Science Foundation of Shanghai(19ZR1405600 and 20ZR1404900)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)。
文摘Chinese,as a logographic language,fundamentally differs from alphabetic languages like English.Previous neuroimaging studies have mainly focused on alphabetic languages,while the exploration of Chinese reading is still an emerging and fast-growing research field.Recently,a growing number of neuroimaging studies have explored the neural circuit of Chinese reading.Here,we summarize previous research on Chinese reading from a connectomic perspective.Converging evidence indicates that the left middle frontal gyrus is a specialized hub region that connects the ventral with dorsal pathways for Chinese reading.Notably,the orthography-to-phonology and orthography-to-semantics mapping,mainly processed in the ventral pathway,are more specific during Chinese reading.Besides,in addition to the left-lateralized language-related regions,reading pathways in the right hemisphere also play an important role in Chinese reading.Throughout,we comprehensively review prior findings and emphasize several challenging issues to be explored in future work.
基金We appreciate the financial support from the National Key Research and Development Program of China(2017YFB1300300)the National Natural Science Foundation of China(62122059,81925020,61976152,and 81630051)the Young Elite Scientist Sponsorship Program by CAST(2018QNRC001).
文摘It has been almost 50 years since the term“brain–computer interface”(BCI)was first proposed by Jacques J.Vidal in 1973[1].Unlike traditional electronic interfaces that transmit nonliving information between devices,BCIs set up a communication bridge between a living brain and nonliving devices.Technically speaking,a BCI is a system that measures brain activity and converts it into the artificial outputs that replace,restore,enhance,supplement,or improve the natural central nervous system outputs[2].At present,electroencephalography(EEG)is the most commonly used brain signal for BCIs.
基金Supported by Karen Elise Jensen`s Foundation and Danish Council for Strategic research,The Danish Agency for Science,Technology and Innovation
文摘Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders.An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive.Consequently,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often ineffective.This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis.Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected cases.In this review,we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis.In addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.
基金supported by the Simons Foundation,the National Natural Science Foundation of China(No.NSFC61405038)the Fujian provincial fund(No.2020J01453).
文摘Neurons can be abstractly represented as skeletons due to the filament nature of neurites.With the rapid development of imaging and image analysis techniques,an increasing amount of neuron skeleton data is being produced.In some scienti fic studies,it is necessary to dissect the axons and dendrites,which is typically done manually and is both tedious and time-consuming.To automate this process,we have developed a method that relies solely on neuronal skeletons using Geometric Deep Learning(GDL).We demonstrate the effectiveness of this method using pyramidal neurons in mammalian brains,and the results are promising for its application in neuroscience studies.
基金supported by the National Key Research and Development Program of China(2017YFB1300302)the National Natural Science Foundation of China(81925020 and61976152)the Young Elite Scientist Sponsorship Program of the China Association for Science and Technology(2018QNRC001)。
文摘The brain function of prediction is fundamental for human beings to shape perceptions efficiently and successively. Through decades of effort, a valuable brain activation map has been obtained for prediction. However,much less is known about how the brain manages the prediction process over time using traditional neuropsychological paradigms. Here, we implemented an innovative paradigm for timing prediction to precisely study the temporal dynamics of neural oscillations. In the experiment recruiting 45 participants, expectation suppression was found for the overall electroencephalographic activity,consistent with previous hemodynamic studies. Notably,we found that N1 was positively associated with predictability while N2 showed a reversed relation to predictability. Furthermore, the matching prediction had a similar profile with no timing prediction, both showing an almost saturated N1 and an absence of N2. The results indicate that the N1 process showed a ‘sharpening' effect for predictable inputs, while the N2 process showed a‘dampening' effect. Therefore, these two paradoxical neural effects of prediction, which have provoked wide confusion in accounting for expectation suppression,actually co-exist in the procedure of timing prediction but work in separate time windows. These findings strongly support a recently-proposed opposing process theory.
基金supported in part by the National Natural Science Foundation of China under Grants 61841103,61673164,and 61602397in part by the Natural Science Foundation of Hunan Provincial under Grants 2016JJ2041 and 2019JJ50106+1 种基金in part by the Key Project of Education Department of Hunan Provincial under Grant 18B385and in part by the Graduate Research Innovation Projects of Hunan Province under Grants CX2018B805 and CX2018B813.
文摘Detecting moving objects in the stationary background is an important problem in visual surveillance systems.However,the traditional background subtraction method fails when the background is not completely stationary and involves certain dynamic changes.In this paper,according to the basic steps of the background subtraction method,a novel non-parametric moving object detection method is proposed based on an improved ant colony algorithm by using the Markov random field.Concretely,the contributions are as follows:1)A new nonparametric strategy is utilized to model the background,based on an improved kernel density estimation;this approach uses an adaptive bandwidth,and the fused features combine the colours,gradients and positions.2)A Markov random field method based on this adaptive background model via the constraint of the spatial context is proposed to extract objects.3)The posterior function is maximized efficiently by using an improved ant colony system algorithm.Extensive experiments show that the proposed method demonstrates a better performance than many existing state-of-the-art methods.
基金The study was supported by the National Key R&D Program of China(2018YFA0701402)the National Natural Science Foundation of China(82021004,81971690,81620108016,and 11835003)the Fundamental Research Funds for the Central Universities of China(2019NTST24).
文摘Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks.However,most resting-state functional magnetic resonance imaging(R-fMRI)studies have identified functional hubs by examining spontaneous fluctuations of the blood oxygen level-dependent signal within a typical low-frequency band(e.g.,0.01–0.08 Hz or 0.01–0.1 Hz).Little is known about how the spatial distributions of functional hubs depend on frequency bands of interest.Here,we used repeatedly measured R-fMRI data from 53 healthy young adults and a degree centrality analysis to identify voxelwise frequency-resolved functional hubs and further examined their test-retest reliability across two sessions.We showed that a wide-range frequency band(0.01–0.24 Hz)accessible with a typical sampling rate(fsample=0.5 Hz)could be classified into three frequency bands with distinct patterns,namely,low-frequency(LF,0.01–0.06 Hz),middle-frequency(MF,0.06–0.16 Hz),and high-frequency(HF,0.16–0.24 Hz)bands.The functional hubs were mainly located in the medial and lateral frontal and parietal cortices in the LF band,and in the medial prefrontal cortex,superior temporal gyrus,parahippocampal gyrus,amygdala,and several cerebellar regions in the MF and HF bands.These hub regions exhibited fair to good test-retest reliability,regardless of the frequency band.The presence of the three frequency bands was well replicated using an independent R-fMRI dataset from 45 healthy young adults.Our findings demonstrate reliable frequency-resolved functional connectivity hubs in three categories,thus providing insights into the frequency-specific connectome organization in healthy and disordered brains.
基金supported by the National Key R&D Program of China (2021ZD0202805,2019YFA0709504,2021ZD0200900)National Defense Science and Technology Innovation Special Zone Spark Project (20-163-00-TS-009-152-01)+4 种基金National Natural Science Foundation of China (31900719,U20A20227,82125008)Innovative Research Team of High-level Local Universities in Shanghai,Science and Technology Committee Rising-Star Program (19QA1401400)111 Project (B18015)Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)Shanghai Center for Brain Science and Brain-Inspired Technology。
文摘Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction.However,action recognition currently used in non-human primate(NHP)research relies heavily on intense manual labor and lacks standardized assessment.In this work,we established two standard benchmark datasets of NHPs in the laboratory:Monkeyin Lab(Mi L),which includes 13 categories of actions and postures,and MiL2D,which includes sequences of two-dimensional(2D)skeleton features.Furthermore,based on recent methodological advances in deep learning and skeleton visualization,we introduced the Monkey Monitor Kit(Mon Kit)toolbox for automatic action recognition,posture estimation,and identification of fine motor activity in monkeys.Using the datasets and Mon Kit,we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of Rett syndrome(RTT).Mon Kit was used to assess motor function,stereotyped behaviors,and depressive phenotypes,with the outcomes compared with human manual detection.Mon Kit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency,thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.
基金This insight article was supported by the National Natural Science Foundation of China(82125032,81901826,81930095,81761128035,81873909,and 82001771)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)+6 种基金the Natural Science Foundation of Shanghai Municipality(19ZR1405600 and 20ZR1404900)the Science and Technology Commission of Shanghai Municipality(19410713500 and 2018SHZDZX01)the Shanghai Municipal Commission of Health and Family Planning(GWV-10.1-XK07,2020CXJQ01,and 2018YJRC03)the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the Guangdong Key Project(2018B030335001)the China Medical Board Open Competition Program(CMB#21-418)ZJLab,and Shanghai Center for Brain Science and Brain-inspired Technology.
文摘Why Was the Cohort Set Up?Autism spectrum disorder(ASD)is a child neurodevelopmental disorder,the onset of which is generally within 3 years of age,and often leads to lifelong impaired social and cognitive functions,which impose significant mental pressure and economic burdens on the family and society.
