Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

Structural changes in pyramidal cell dendrites and synapses in the unaffected side of the sensorimotor cortex following transcranial magnetic stimulation and rehabilitation training in a rat model of focal cerebral infarct

Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.

Non-concomitant cortical structural and functional alterations in sensorimotor areas following incomplete spinal cord injury

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury（SCI）. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI（mean age 40.94 ± 14.10 years old; male：female, 7：11） and 18 healthy subjects（37.33 ± 11.79 years old; male：female, 7：11） were studied by resting state functional magnetic resonance imaging. Gray matter volume（GMV） and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex（BA1） and left primary motor cortex（BA4）, and left BA1 and left somatosensory association cortex（BA5） was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-ROC-17013566）.

Detection of Ca^(2+)-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin

The study aims to confirm the neuroregenerative effects of bacterial melanin （BM） on central nervous system injury using a special staining method based on the detection of Ca^2＋-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex （group I; n = 12） or unilateral rubrospinal tract transection at the cervical level （C3-4） （group II; n = 12）. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution （BM subgroup） and the remaining six rats were intramuscularly in）ected with saline （saline subgroup）. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca^2＋-dependent acid phosphatase activity detection in combination with Chilingarian＇s calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca^2＋-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.

Changes in sensorimotor regions of the cerebral cortex in congenital amusia:a case-control study

Perceiving pitch is a central function of the human auditory system;congenital amusia is a disorder of pitch perception.The underlying neural mechanisms of congenital amusia have been actively discussed.However,little attention has been paid to the changes in the motor rain within congenital amusia.In this case-control study,17 participants with congenital amusia and 14 healthy controls underwent functional magnetic resonance imaging while resting with their eyes closed.A voxel-based degree centrality method was used to identify abnormal functional network centrality by comparing degree centrality values between the congenital amusia group and the healthy control group.We found decreased degree centrality values in the right primary sensorimotor areas in participants with congenital amusia relative to controls,indicating potentially decreased centrality of the corresponding brain regions in the auditory-sensory motor feedback network.We found a significant positive correlation between the degree centrality values and the Montreal Battery of Evaluation of Amusia scores.In conclusion,our study identified novel,hitherto undiscussed candidate brain regions that may partly contribute to or be modulated by congenital amusia.Our evidence supports the view that sensorimotor coupling plays an important role in memory and musical discrimination.The study was approved by the Ethics Committee of the Second Xiangya Hospital,Central South University,China(No.WDX20180101GZ01)on February 9,2019.

Aberrant Light-Induced Depression is Associated with Impaired Sensorimotor Gating in Mice

Mice subjected to an irregular light-dark cycle are known to lose their capacity to synchronize their behavioral rhythm to environmental light, and to show endophenotypes related to depressive disorders. Here we observed that a susceptible strain of mice (C3H/HeJ) subjected to an irregular 3.5 hr:3.5 hr light-dark cycle showed an enhanced acoustic startle reflex and deficits in prepulse inhibition. As impaired sensorimotor gating is associated with the onset of a variety of mental disorders such as schizophrenia and major depressive disorder, irregular environmental light without circadian photo-entrainment may cause stress that has the potential to be involved in humans’ susceptibility to neuropsychiatric abnormalities.

Warm-needle acupuncture for limb spasticity post-stroke:a systematic review

Background:Warm acupuncture,or warm-needle acupuncture,is a traditional external treatment widely used in China for thousands of years.However,the effects of different treatment times on limb spasticity post-stroke have not been evaluated.Methods:We searched PubMed,Embase,the Cochrane Library,the Web of Science,the China National Knowledge Infrastructure,the Chinese Scientific and Journal Database,the Wanfang database,and the Chinese Biomedical Literature Database from inception to May 21st,2020,to seek information regarding randomized controlled trials studying warm-needle acupuncture for limb spasticity post-stroke.Two authors selected 24 studies fitting the eligibility criteria and developed this systematic review and meta-analysis.Results:Warm-needle acupuncture is shown to be more effective than other treatments used in the control groups(odds ratio(OR)=3.61,95%confidence intervals(CI)(2.51,5.19),P<0.001).This treatment decreased limb spasticity as assessed with the Modified Ashworth Scale(mean differences(MD)=−0.78,95%CI(−1.00,−0.56),P<0.001)and the Clinic Spasticity Index(MD=1.06,95%CI(0.51,1.60),P=0.0002),improved sensorimotor impairments according to the Fugl-Meyer Assessment(MD=9.51,95%CI(6.99,12.03),P<0.001),and improved activities of daily living according to the Barthel Index(MD=9.70,95%CI(6.27,13.12),P<0.001).Subgroup analysis based on the length of the treatment using the Modified Ashworth Scale,Fugl-Meyer Assessment,and Barthel Index showed better outcomes for patients who received more than 20 days of treatments(P<0.001).Conclusion:Warm-needle acupuncture is an effective treatment for limb spasticity post-stroke.A treatment frequency of more than 20 days appears to have better effectiveness than that of less than 20 days.

Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.

完全性脊髓损伤早期患者脑皮层结构变化的磁共振研究

目的：观察完全性脊髓损伤（SCI）患者在损伤早期大脑皮层结构是否存在改变及其与患者感觉运动功能损伤程度的相关性.方法：2013年10月～2013年12月在北京军区总医院骨科住院的13例完全性SCI患者被纳入研究,其中男7例,女6例,年龄26.3±7.9岁（21～40岁）.同时招募健康对照15例,其中男8例,女7例,年龄25.7±5.8岁（20～38岁）.SCI患者损伤时间为64.4±20.3d（28～84d）.13例患者脊髓功能用美国脊髓损伤协会（ASIA）分级标准评定均为A级,其中ASIA运动评分为36.5±25.9（18～55）分,针刺觉评分为43.3±27.3（27～88）分,轻触觉评分为42.5±30.3（25～80）分.所有SCI患者在入院当天接受结构MRI检查.MRI扫描后的结构数据用基于体素形态学分析的方法（VBM）来分析,对比分析13例完全性SCI患者和15例年龄、性别相匹配的健康对照者大脑灰质体积改变的区域.运用Person相关性分析探讨脑皮层结构改变与患者运动感觉功能之间的关系.结果：与健康对照者相比,完全性SCI患者初级运动中枢、初级躯体感觉中枢和辅助运动区存在明显的灰质萎缩（P＜0.05）.相关性分析显示完全性SCI患者上述区域萎缩程度与患者的ASIA运动评分以及ASIA感觉评分无明显相关性（P＞0.05）.结论：在损伤早期,完全性SCI患者初级运动中枢、初级躯体感觉中枢和辅助运动区存在明显的灰质萎缩,上述区域萎缩程度与患者的ASIA评分无明显相关性.

两轮机器人具有内发动机机制的感知运动系统的建立

针对两轮机器人运动平衡控制问题,为其建立起一种人工感知运动系统TWR-SMS(Two-wheeled robot sensorimotor system),使机器人在与环境的接触过程中可以通过学习自主掌握运动平衡技能.感知运动系统的认知系统以学习自动机为数学模型,引入好奇心和取向性概念,设计了能够主动探索环境以及主动学习环境的内发动机机制.实验结果证明内发动机机制的引入不仅提高了机器人的自学习和自组织特性,同时能够有效避免小概率事件的发生,稳定性较高.与传统线性二次型调节器(Linear quadratic regulator,LQR)控制方法的对比实验表明系统具有更好的鲁棒性.

基于内发动机机制的机器人趋光控制

针对移动机器人的趋光问题,提出了一种基于内发动机机制的控制方法.该方法以生物体感觉运动系统的学习机制为基础,通过评价、行为选择以及取向和决策环节的强化实现对机器人最优趋光控制策略的搜索,使机器人在未知环境下,通过自主的学习和训练,逐渐掌握趋光移动技能.采用马尔科夫定理证明了学习过程的收敛性;仿真实验证明了基于内发动机机制趋光控制方法的有效性;通过与人工势场法的比较,说明了该方法的精确性.

大鼠感觉运动系统静息态脑网络研究

为了理解啮齿类动物的脑功能连接,本文利用9.4T fMRI获得轻度麻醉状态下大鼠静息状态及刺激激活的数据,通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数.结果发现:给予前爪电刺激时,刺激对侧初级感觉皮层(S1)、丘脑(Tha)有较强的正激活,双侧尾状壳核(CPu)有较强的负激活.静息状态时大鼠感觉/运动皮层内部、丘脑内部的连接性较强,而感觉/运动皮层与丘脑之间的连接较弱,双侧感觉运动系统之间存在较强的同步低频振荡,感觉运动系统在静息态时的脑网络具有小世界属性.结果提示,啮齿类动物在大脑信息处理中的功能分离和整合可能与人类存在某些相似性,支持哺乳动物中枢神经系统的基本功能存在遗传保守性的观点.

一种基于情感智能的机器人自主趋光行为研究

针对移动机器人的自主趋光行为问题,提出了一种基于情感智能的内发动机仿生学习机制。该学习机制以生物体感觉运动系统的学习机制为基础,包括评价环节、行为选择环节和取向环节,采用模糊神经网络构建情感模型,情感模型的输出作为评价环节的内部奖赏信号。该学习机制能够使机器人在未知环境下通过自主的学习和训练逐渐形成、发展和完善趋光行为技能,通过情感智能的作用可以增加试探成功次数和减小学习步数,仿真实验证明了该方法的有效性。

用于机器人运动控制的通用小脑认知模块的构建

用具有神经生理学性质的小脑模型实现对机器人系统各种不同感觉协调运动的控制,这是当前机器人控制领域的一个研究热点。但针对一种控制任务就要构建一种对应的小脑模型,这种方式效率很不理想。文中以运动控制为基础,构建了一种包括所有主要细胞类型及其连接的通用小脑认知模块(General Cerebellum CognitiveModule,GCCM)。对给定的背景知识,GCCM能够通过学习生成理想输出,因而,可用于各种不同的机器人感觉运动控制任务。仿真实验证明,通过将脊髓层次上的轨迹误差检测与小脑中的记忆轨迹结合起来,嵌入的GCCM控制系统能对快速手臂延伸运动进行精确的鲁棒控制。

认知神经模拟对二语习得的启示

认知科学认为认知是一种生物学现象,与身体的其他系统共同进化,并且源自人类与环境的交互作用。有机体的生物特性以及有机体所处的物理环境与社会环境都会对认知起到重要的作用。因此,语言、认知及思维不仅根植于有机体的身体性,而且也根植于有机体的感觉运动系统。本文以认知科学研究为理论背景,阐释语言认知神经模拟理论,试图揭示语言背后的认知神经机制及模拟系统,并且对二语习得研究具有启示性作用。

基于应激系统理论的护理模式联合感觉运动训练对脑梗死恢复期患者的应用

目的分析基于应激系统理论的护理模式联合感觉运动训练(SMT)在脑梗死(CI)恢复期患者中的应用效果。方法前瞻性选取2019年1月至2020年1月青岛市市立医院接收的80例CI恢复期患者为研究对象,根据病历单双号分组。单号患者纳为对照组(40例),实施常规护理联合SMT;双号患者纳为观察组(40例),实施常规护理+基于应激系统理论的护理联合SMT,干预至出院结束(住院时间为21~28 d)。于干预前、出院前1 d,比较两组下肢运动功能[采用简式Fugl-Meyer评估量表(FMA)]、平衡能力[采用Berg平衡量表(BBS)评估]、创伤后成长(PTG)[采用PTG评定量表(PTGI)评估]等情况。结果出院前1 d,两组下肢FMA评分、BBS评分、PTGI评分高于干预前,且观察组各评分高于对照组,差异有统计学意义(P<0.05)。结论基于应激系统理论的护理模式联合SMT应用于CI恢复期患者中,利于提高患者下肢运动功能及平衡能力,对提高患者PTG具有积极意义。

具身认知理论下的二语习得

具身认知理论认为人的认知过程根植于感觉运动系统,身体体验在认知中发挥着重要的作用。一系列的一语研究表明,感觉运动系统对于语言理解也起着重要的作用。二语的习得是在一语概念系统的基础上形成的一种新的概念系统,感觉运动系统在二语习得的过程中具有何种作用,程度如何?本文总结了近年来关于二语加工中的具身效应、一语和二语具身效应之间联系的实证研究,归纳了影响二语具身效应加工的主要因素。最后指出未来的研究应该着眼于探究在不同影响因素下二语具身效应的具体表现,进而探究二语加工中感觉运动系统和符号加工系统所占权重以及感觉运动系统在二语加工中的充分性和必要性。

Effects of 16-week Tai Chi intervention on postural stability and associated physiological factors in older people

Objectives:To examine the effects of 16-week Tai Chi(TC) training on postural stability and associated physiological factors in older subjects,forty elderly individuals(aged ≥ 60 years) living in the community were randomly placed into either the TC intervention group(n=22) or the control group(n=18).The former underwent a supervised TC exercise program for 16 weeks,while the latter received general education for a comparable time period.Measurements:Postural stability was assessed by timed stance tests in single-leg stance with the eyes open(SLO) or closed(SLC),and tandem stance with the eyes closed(TSC).Proprioceptive function was evaluated by measuring ankle and knee kinesthesia.The maximum concentric strength of the knee flexors and extensors,ankle plantarflexors and dorsiflexors was measured by isokinetic dynamometer.Moreover,the reaction time of different muscles in the lower extremity was also examined by measuring the onset latency of the muscles to perturbations on the ankle joint using an electromyography system.Results:After the 16-week TC intervention,significant TC training effects were gained on knee kinesthesia,knee flexor strength,latency of semitendinous muscle,and postural stability in SLO.For the other measures,no significant training effects were found.Conclusions:The 16-week TC intervention was found to be beneficial for the improvement of postural stability and associated physiological factors.However,there are discrepancies in TC training effects on different factors in the sensorimotor system.

Motor Control Network Effective Connectivity in Regulating Muscle Force Output

Objective of the study: This study aimed at characterizing output features of the higher-order motor control centers (hoMCCs), including secondary (premotor cortex [Pre] and supplementary motor area [SMA]) and association (prefrontal cortex [PFC]) motor regions to the primary motor cortex (M1) during graded force tasks. It is well known that one of the major roles of the primary motor cortex (M1) is controlling motor output such as muscle force. However, it is unclear how the hoMCCs interact with M1 in regulating voluntary muscle contractions. Methods: fMRI data was acquired during graded force tasks and fMRI-based effective connectivity (EC) and muscle force analyses were performed to study the relationship between hoMCCs-M1 effective connectivity and voluntarily exerted handgrip force. Results: The results show that there is a consistent information flow from the hoMCCs to M1 under all force conditions, suggesting a hierarchical control mechanism in the brain in regulating voluntary muscle force. Only the premotor cortex exhibited a significant role in mediating the level of force production through its EC with M1 but that role diminished when the exerted force was high, suggesting perhaps a ceiling and/or fatigue effect on the EC. A flip in the direction of EC from the primary sensory cortex (S1) to the hoMCCs (PFC, SMA, and Pre) at lower force levels while at higher forces EC was observed from the hoMCCs to S1. Conclusion: The hoMCCs regulate M1 output to produce desired voluntary muscle force. Only the Pre-to-M1 connectivity strength directly correlates with the force level especially from low to moderate levels. The hoMCCs are involved in modulating higher force production likely by strengthening M1 output and downgrading inhibition from S1 to M1.

舞蹈运动员大脑感知运动系统的功能特征——一项静息态功能磁共振研究

目的:探索经过长期专项练习的舞蹈运动员大脑感知运动系统的功能特征。方法:采用专家-新手研究范式,选取具有6年以上专业舞蹈练习经历的23名舞者作为舞蹈组,未经过任何舞蹈练习的21名大学生作为对照组。采集被试的静息态功能磁共振数据,比较两组被试的局部一致性(Re Ho)、比率低频振幅(f ALFF)和功能连接(FC)。结果:1)舞蹈组双侧中央后回、左侧颞上回、右侧中央前回、右侧枕中回Re Ho值显著高于对照组;2)舞蹈组双侧中央前回f ALFF值显著高于对照组;3)舞蹈组右侧中央前回与左侧中央前回的连接强度及右侧中央前回与双侧中央后回的FC值均显著高于对照组。结论:舞者感知运动系统功能改变可能与长期舞蹈练习相关,这可能会导致个体的感知、记忆加工及动作学习与控制能力发生改变,建立对复杂动作良好的观察、执行和调整的加工模式,这一结果为舞蹈练习促进大脑可塑性提供了证据支持。