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Multivariate time series (MTS) data exist in various fields of studies and MTS classification is an important research topic in the machine learning community. Researchers have proposed many MTS classification models over the years and the distance-based methods along with nearest neighbor classifier achieve good performance. However, the current methods mainly focus on defining distance metric on time-domain of MTS and ignore frequency information. Besides, these methods usually define the same linear distance metric for different datasets, which is not suitable for capturing the nonlinear relationship of MTS and degrades the discriminative power of the distance metric. In this paper, we propose a time–frequency deep metric learning (TFDM) approach for MTS classification. The multilevel discrete wavelet decomposition is first adopted to decompose an MTS into a group of sub-MTS so as to extract multilevel time–frequency representations. Then, a deep convolutional neural network is developed for each level to learn level-specific nonlinear features and a metric learning layer is added on the top of the network to learn the semantic similarity of MTS. Moreover, a cross-level consistency regularization term is designed to encourage the distance metrics of different levels to be consistent for capturing the correlations among different levels. Finally, we use 1-nearest neighbor to classify MTS according to the learned distance metrics. Extensive experiments on 18 benchmark datasets show the effectiveness of our approach.

BACKGROUND Early detection of mild cognitive impairment (MCI) symptoms is an important step to the subsequent medical diagnostic and intervention. We developed a new screening test called the Efficient Online MCI Screening System (EOmciSS) for use in community-dwelling older adults. It is a self-paced rapid cognitive test to be completed within 10 minutes on tablets or mobile phones in homes or elderly centers. OBJECTIVE This study was aimed to test the validity of the EOmciSS for identifying community-dwelling older adults with MCI risks. METHODS The participants (N=827) completed the EOmciSS and other criterion instruments. The evidence of the psychometric properties included subscale item difficulty, discriminative index, internal consistency, and construct validity. We further tested the between-group discrimination using cross-validation method on the labelled MCI and normal cognitive groups. RESULTS Three accuracy and one reaction time factors explained the structure of the 20 item factors. Difficulty levels of the item factors in the accuracy factors, namely Trail Making, Clock Drawing and Cube Copying, and Delayed Recall were 0.63 to 0.99; while those of the reaction time factor were 0.77 to 0.95. Discriminative indices of the medium to high difficulty item factors were ranged from 0.39 to 0.97. The internal consistency indices (Cronbach’s Alpha) ranged from 0.41 (for few item factor) to 0.96. Training dataset indicated nine item factors as the significant predictors for the MCI versus NC classification. Presence of depressive symptoms was identified as a significant factor influencing participants’ performance, which was an integral part of the test system. Age, education level and proficiency level of using electronic device of the participants did not significantly influence their scores and classification. Application of the MCI/NC cut off score (7.90 out of 9,67) to the validation dataset yielded an AUC value of 0.912 (P < .001) (95% C.I. 0.868-0.955). The sensitivity and specificity were 84.9% and 85.1% respectively, and the Youden index was 0.70. CONCLUSIONS The EOmciSS shows satisfactory evidence on its validity and reliability for identifying older adults with significant risks of MCI. The user-interface, online operation and self-paced format allow the test system to be operated by older adult users or their caregivers in different community settings such as home and elderly centers. Depressive symptoms, found influencing the test performances and hence the MCI risks, should be an integral part in future MCI screening system. CLINICALTRIAL Chinese Clinical Trial Registry ChiCTR2000039411

ImportanceType 2 diabetes (T2D) is associated with the progression of cognitive dysfunction. Physical activity benefits cognition, but no evidence from randomized clinical trials has shown whether tai chi chuan has better long-term benefits than fitness walking in cognitive function for patients with T2D and mild cognitive impairment (MCI).ObjectiveTo compare the effectiveness of tai chi chuan, a mind-body exercise, for improving cognitive function in older adults with T2D and MCI, with fitness walking.Design, Setting, and ParticipantsThis randomized clinical trial was conducted between June 1, 2020, and February 28, 2022, at 4 sites in China. Participants included 328 adults (aged ≥60 years) with a clinical diagnosis of T2D and MCI.InterventionsParticipants were randomized in a 1:1:1 ratio to a tai chi chuan group, a fitness walking group, or a control group. The tai chi chuan group received 24-form simplified tai chi chuan. The fitness walking group received fitness walking training. Both exercise groups took the training for 60 min/session, 3 times/wk, for 24 weeks in a supervised setting. All 3 groups were provided with a 30-minute diabetes self-management education session, once every 4 weeks for 24 weeks. The participants were followed up for 36 weeks.Main Outcomes and MeasuresThe primary outcome was the global cognitive function measured at 36 weeks by the Montreal Cognitive Assessment (MoCA). Secondary outcomes included MoCA at 24 weeks and other cognitive subdomain measures and blood metabolic indices at 24 and 36 weeks.ResultsA total of 328 participants (mean [SD] age, 67.55 [5.02] years; mean [SD] T2D duration, 10.48 [6.81] years; 167 [50.9%] women) were randomized to the tai chi chuan group (n = 107), fitness walking group (n = 110), or control group (n = 111) and included in the intention-to-treat analysis. At 36 weeks, the tai chi chuan group showed improved MoCA scores compared with the fitness walking group (mean [SD], 24.67 [2.72] vs 23.84 [3.17]; between-group mean difference, 0.84 [95% CI, 0.02-1.66]; P = .046) in the intention-to-treat analysis. The per-protocol analysis data set and subgroup analysis at 36 weeks showed similar results. Based on the generalized linear models, the treatment effects were similar in each group after adjusting for self-reported dietary calories and physical activity. There were 37 nonserious adverse events (tai chi chuan group, 8; fitness walking group, 13; control group, 16) unrelated to the study with no statistically significant difference among the 3 groups (P = .26).Conclusions and RelevanceIn this randomized clinical trial including older adults with T2D and MCI, tai chi chuan was more effective than fitness walking in improving global cognitive function. The findings support a long-term benefit, suggesting the potential clinical use of tai chi chuan as an exercise intervention to improve cognitive function for older adults with T2D and MCI.Trial RegistrationClinicalTrials.gov Identifier: NCT04416841

The uniqueness of neural processes between allocentric and egocentric spatial coding has been controversial. The distinctive paradigms used in previous studies for manipulating spatial coding could have attributed for the inconsistent results. This study was aimed to generate converging evidence from previous functional brain imaging experiments for collating neural substrates associated with these two types of spatial coding. An additional aim was to test whether test-taking processes would have influenced the results. We obtained coordinate-based functional neuroimaging data for 447 subjects and performed activation likelihood estimation (ALE) meta-analysis. Among the 28 experiments, the results indicate two common clusters of convergence. They were the right precuneus and the right superior frontal gyrus as parts of the parieto-frontal circuit. Between-type differences were in the parieto-occipital circuit, with allocentric showing convergence in the superior occipital gyrus (SOG) cluster compared with egocentric showing convergence in the middle occipital gyrus (MOG) cluster. Task-specific influences were only found in allocentric spatial coding. Spatial judgment-oriented tasks seem to increase the demands on manipulating spatial relationships among the visual objects, while spatial navigation tasks seem to increase the demands on maintaining object representations. Our findings address the theoretical controversies on spatial coding that both the allocentric and egocentric types are common in their processes mediated by the parieto-frontal network, while unique and additional processes in the allocentric type are mediated by the parieto-occipital network. The positive results on possible task-specific confound offer insights into the future design of spatial tasks for eliciting spatial coding processes.

Objective: Chronic cerebral ischemia leads to vascular cognitive impairment (VCI) that exacerbates along with ischemia time and eventually develops into dementia. Recent advances in molecular neuroimaging contribute to understand its pathological characteristics. We previously traced the anisotropic diffusion of water molecules suggests that chronic cerebral ischemia leads to irreversible progressive damage to white matter integrity. However, the abnormalities of gray matter activity following chronic cerebral ischemia remains not entirely understood.Methods: In this study, in vivo hydrogen proton magnetic resonance spectroscopy (1H-MRS) was applied to longitudinally track the neurochemical metabolic disorder of gray matter associated with working memory, and optogenetics modulation of neurochemical metabolism was performed for targeted treatment of VCI. Results: The results showed that the concentration of N-acetylaspartate (NAA) in the right hippocampus, left hippocampus, right medial prefrontal cortex (mPFC) and mediodorsal thalamus was decreased as early as 7 days after chronic cerebral ischemia, subsequently gamma-aminobutyric acid (GABA) declined whereas myo-inositol (mI) and glutamate (Glu) increased at 14 days, as well as choline (Cho) lost at 28 days, concurrently the change of Glu and GABA in the mPFC and hippocampus was ischemia time-dependent manner within 1 month. Behaviorally, working memory and object recognition memory were impaired at 14 days, 28 days that significantly correlated with neurochemical metabolic disorders. Interestingly, using optogenetics modulation of PV neurons in the mPFC, the metabolic abnormalities of NAA and GABA in working memory neural circuit could be repaired after chronic cerebral ischemia, together with behavior improvements. Conclusions: These findings suggested that as early as 1~4 weeks after chronic cerebral ischemia, the metabolism of NAA, Glu, mI and Cho was synchronously impaired in neural circuit of hippocampus-mediodorsal thalamus-mPFC, and the loss of GABA delayed in the hippocampus, and optogenetics modulation of parvalbumin (PV) neurons in the mPFC can improve the neurochemical metabolism of working memory neural circuit and enhance working memory.

Based on the theory of interhemispheric inhibition and the bimodal balance-recovery model in stroke, we explored the effects of excitation/inhibition (E/I) of parvalbumin (PV) neurons in the contralateral primary motor cortex (cM1) connecting the ipsilateral M1 (iM1) via the corpus callosum (cM1-CC-iM1) of ischemic stroke rats by optogenetic stimulation.We tested this by injecting anterograde and retrograde virus in rats with middle cerebral artery occlusion (MCAO), and evaluated the neurological scores, motor behavior, volume of cerebral infarction and the E/I balance of the bilateral M1 two weeks after employing optogenetic treatment.We found that concentrations of Glu and GABA decreased and increased, respectively, in the iM1 of MCAO rats, and that the former increased in the cM1, suggesting E/I imbalance in bilateral M1 after ischemic stroke. Interestingly, optogenetic stimulation improved M1 E/I imbalance, as illustrated by the increase of Glu in the iM1 and the decrease of GABA in both iM1 and cM1, which were accompanied by an improvement in neurological deficit and motor dysfunction. In addition, we observed a reduced infarct volume, an increase in the expression of the NMDAR and AMPAR, and a decrease in GAD67 in the iM1 after intervention.Optogenetic modulation of PV neurons of the iM1-CC-cM1 improve E/I balance, leading to reduced neurological deficit and improved motor dysfunction following ischemic stroke in rats.

Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of brain capillaries is triggered by beta-amyloid (Aβ) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating Aβ plaque deposition, the primary pathophysiology of Alzheimer’s disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while Aβ plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early Aβ plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated Aβ plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating Aβ plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01024-7.

Allocentric and egocentric are two types of spatial coding. Previous studies reported the dorsal attention network's involvement in both types. To eliminate possible paradigm-specific confounds in the results, this study employed fine-grained cue-to-target paradigm to dissociate allocentric (aSC) and egocentric (eSC) spatial coding. Twenty-two participants completed a custom visuospatial task, and changes in the concentration of oxygenated hemoglobin (O2-Hb) were recorded using functional near-infrared spectroscopy (fNIRS). The least absolute shrinkage and selection operator-regularized principal component (LASSO-RPC) algorithm was used to identify cortical sites that predicted the aSC and eSC conditions' reaction times. Significant changes in O2-Hb concentration in the right inferior parietal lobule (IPL) and post-central gyrus regions were common in both aSC and eSC. Results of inter-channel correlations further substantiate cortical activities in both conditions were predominantly over the right parieto-frontal areas. Together with right superior frontal gyrus areas be the reaction time neural correlates, the results suggest top-down attention and response-mapping processes are common to both spatial coding types. Changes unique to aSC were in clusters over the right intraparietal sulcus, right temporo-parietal junction, and left IPL. With the left pre-central gyrus region, be the reaction time neural correlate, aSC is likely to involve more orienting attention, updating of spatial information, and object-based response selection and inhibition than eSC. Future studies will use other visuospatial task designs for testing the robustness of the findings on spatial coding processes.

Background. The clinical efficacy of temporal three-needle therapy for stroke dysfunction has been previously demonstrated in China. However, the central mechanism of temporal three-needle therapy remains unclear. Temporal three-needle projects the sensory cortex and the motor cortex, which may impact the cortex function. Current studies seldom focus on it. Hence, according to the “scalp-cortex corresponding theory,” the underlying mechanism of temporal three-needle remains a domain for further research. Methods. This trial is designed to provide objective and visual evidence for the neuromodulatory effect and neuroimaging mechanism of temporal three-needle therapy for stroke patients. This ongoing study is a prospective, randomized, controlled, patient-assessor blind, single-center, neuroimaging trial involving two-parallel patient groups and a healthy control group. Forty eligible patients will be recruited from Shenzhen Nanshan District People’s Hospital and randomized into either the experimental group or the control group. Twenty healthy volunteers will be recruited in the healthy control group and undergo baseline magnetic resonance imaging scans without any intervention. Patients in the control group will receive acupuncture at Dingnieqianxiexian (MS6), in addition to basic medicine and rehabilitative treatments. Patients in the experimental group will receive temporal three-needle therapy plus basic medicine and rehabilitative treatments 5 days per week, 10 sessions over two consecutive weeks. The primary outcome is resting-state functional connectivity, and the secondary outcomes are regional homogeneity, amplitude of low-frequency fluctuations, Fugl–Meyer assessment of the upper limb, and modified Barthel Index. All outcome measures will be assessed at baseline and after 2 weeks of intervention. Discussion. The results will explore the neuromodulatory effects and illustrate the central mechanism of temporal three-needle treatment from the network-level viewpoint of sensorimotor network functional plasticity and promote widespread application in real-world practice. This trial was registered at Chinese Clinical Trial Registry on 14 March 2018 with ChiCTR1800015209.

Stress is an inevitable element of everyday living. Developmental studies suggested that adolescents are more vulnerable and sensitive to the effect of stress due to their developing brains, especially in areas related to stress perception and processing. This voxel-based morphometry study examined the association between various neurobiological markers and the level of perceived stress experienced by adolescents (n = 26) and middle-aged adults (n = 26). Our findings indicated that differences existed in the relationships between perceived stress and the structural volume of the orbitofrontal cortex (OFC) extending to the insula and amygdala. Specifically, the levels of perceived stress and the grey matter volume of the orbitofrontal cortex, the insula, and the amygdala were positively related in adolescents but negatively related for adults. Furthermore, a significant negative correlation between perceived stress and cortisol levels was observed in adults, whereas the relationship between perceived stress and cortisol levels was not significant for adolescents. Perceived stress measurement may be better than cortisol levels in terms of reflecting the emotional states of adolescents. In sum, the relationships between perceived stress and neurobiological markers were different between adolescents and middle-aged adults and thus appeared to be age dependent.

Background To evaluate whether electroacupuncture (EA) treatment at LI11 and ST36 could reduce motor impairments and enhance brain functional recovery in a rat model of ischemic stroke. Methods A rat model of middle cerebral artery occlusion (MCAO) was established. EA at LI11 and ST36 was started at 24 h (MCAO + EA group) after ischemic stroke modeling. Untreated model (MCAO) and sham-operated (Sham) groups were included as controls. The neurological deficits of all groups were assessed using modified neurologic severity scores (mNSS) at 24 h and 14 days after MCAO. To further investigate the effect of EA on infarct volume and brain function, functional magnetic resonance imaging was used to estimate the size of the brain lesions and neural activities of each group at 14 days after ischemic stroke. Results EA treatment of MCAO rats led to a significant reduction in the infarct volumes accompanied by functional recovery, reflected in improved mNSS outcomes and motor functional performances. Furthermore, functional connectivity between the left motor cortex and left cerebellum posterior lobe, right motor cortex, left striatum and bilateral sensory cortex were decreased in MCAO group but increased after EA treatment. Conclusion EA at LI11 and ST36 could enhance the functional connectivity between the left motor cortex and the motor function-related brain regions, including the motor cortex, sensory cortex and striatum, in rats. EA exhibits potential as a treatment for ischemic stroke.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with clinical, biological, and pathological features occurring along a continuum from normal to end-stage disease. Currently, the diagnosis of AD depends on clinical assessments and post-mortem neuropathology, which is unbenefited early diagnosis and progressive monitoring. In recent years, clinical studies have reported that the level of cerebrospinal fluid (CSF) and blood neurogranin (Ng) are closely related to the occurrence and subsequent progression of AD. Therefore, the study used meta-analysis to identify the CSF and blood Ng levels for the development of diagnosis biomarker of patients with AD and mild cognitive impairment (MCI). We searched the Pubmed, Embase, Cochrane Library, and Web of Science databases. A total of 24 articles eligible for inclusion and exclusion criteria were assessed, including 4661 individuals, consisting of 1518 AD patients, 1501 MCI patients, and 1642 healthy control subjects. The level of CSF Ng significantly increased in patients with AD and MCI compared with healthy control subjects (SMD: 0.84 [95% CI: 0.70–0.98], P P = 0.008), and higher in AD patients than in MCI patients (SMD: 0.18 [95% CI: 0.07–0.30], P = 0.002), and CSF Ng level of patients with MCI-AD who progressed from MCI to AD was significantly higher than that of patients with stable MCI (sMCI) (SMD: 0.71 [95% CI: 0.25–1.16], P = 0.002). Moreover, the concentration of Ng in blood plasma exosomes of patients with AD and MCI was lower than that of healthy control subjects (SMD: −6.657 [95% CI: −10.558 to −2.755], P = 0.001; and SMD: −3.64 [95% CI: −6.50 to −0.78], P = 0.013), and which in patients with AD and MCI-AD were also lower than those in patients with sMCI (P P = 0.047). Therefore, the Ng levels increased in CSF, but decreased in blood plasma exosomes of patients with AD and MCI-AD, and highly associated with cognitive declines. These findings provide the clinical evidence that CSF and blood exosomes Ng can be used as a cognitive biomarker for AD and MCI-AD, and further studies are needed to define the specific range of Ng values for diagnosis at the different stages of AD.

Chronic loneliness predicts mood disturbances and onset of major depressive disorder. However, little research has examined the neural correlates of individual difference in susceptibility to perceiving loneliness. In addition, the role of cerebellum, which is heavily implicated in social, cognitive and affective processes, in loneliness is unclear. We studied 99 healthy individuals divided into susceptible, concordant and robust groups depending on whether the participant’s loneliness level was greater, comparable or less than her/his objective social isolation level. The cerebellar gray matter structure, functional activity and connectivity patterns during performing an emotion stroop task were examined. We found greater posterior and medial cerebellar volume in the susceptible group than the other groups. In addition, the posterior and medial cerebellar activities when processing positive versus neutral words exhibited significant interactive effects of both loneliness and social network, and susceptibility to isolation. Loneliness and social network also had positive effects on the right posterior cerebellar functional connectivity with the visual and premotor cortices. Our findings provide novel evidence on the intricate role of the cerebellum in loneliness and susceptibility to isolation, suggesting that socio-cognitive processes of the cerebellum in the hedonic domain may be a key mechanism underlying loneliness proneness. Electronic supplementary material The online version of this article (10.1007/s00429-019-01965-y) contains supplementary material, which is available to authorized users.

Background Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis. Methods We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis. Results Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups. Conclusions Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain. Clinical trial registration ChiCTR-IOR-16009308.

This study investigated the effects of Tai Chi compared with no exercise control on the cerebral hemodynamic parameters and other health-related factors in community older adults at risk of ischemic stroke. A total of 170 eligible participants were randomly allocated to Tai Chi or control group. The cerebral hemodynamic parameters and physical fitness risk factors of cardiovascular disease were measured at baseline, 12 weeks, and 24 weeks. After the 12-week intervention, Tai Chi significantly improved the minimum of blood flow velocity (BFVmin); BFVmean; pulsatility index and resistance index of the right anterior cerebral artery; and BFVmax, BFVmin, and BFVmean parameters of the right middle cerebral artery. Tai Chi training also decreased triglyceride, fasting blood glucose, and homocysteine levels, and improved balance ability. Therefore, the supervised 12-week Tai Chi exercise had potential beneficial effects on cerebral hemodynamics, plasma risk factors, and balance ability in older community adults at risk of ischemic stroke.

Aerobic glycolysis (AG), an important pathway of glucose metabolism, is dramatically declined in Alzheimer’s disease (AD). AMP-activated protein kinase (AMPK) is a key regulator to maintain the stability of energy metabolism by promoting the process of AG and regulating glucose metabolism. Interestingly, it has been previously reported that electroacupuncture (EA) treatment can improve cognitive function in AD through the enhancement of glucose metabolism. In this study, we generated AMPK-knockdown mice to confirm the EA effect on AMPK activation and further clarify the mechanism of EA in regulating energy metabolism and improving cognitive function in APP/PS1 mice. The behavioral results showed that EA treatment can improve the learning and memory abilities in APP/PS1 mice. At the same time, the glucose metabolism in the hippocampus was increased detected by MRI-chemical exchange saturation transfer (MRI-CEST). The expression of proteins associated with AG in the hippocampus was increased simultaneously, including hexokinase II (HK2), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), and pyruvate kinase M2 (PKM2). Moreover, the knockdown of AMPK attenuated AG activated by EA treatment. In conclusion, this study proves that EA can activate AMPK to enhance the process of AG in the early stage of AD.

Accumulated evidence has proved that both neuroinflammation and neuroprotection existing at the stage of mild cognitive impairment (MCI) may mediate its progression, which can conversely be modulated by physical activity (PA). However, further research is needed to clarify which factors are involved in that process.To identify the impact of PA on inflammatory cytokines and neuroprotective factors in individuals with MCI.Four databases [PubMed, Cochrane Library, Cochrane Library (Trials), Embase and Web of Science Core Collection] were searched from their inception to October 2021 for randomized-controlled trials (RCTs) assessing the biochemical effect of PA on biomarkers in participants with MCI. Pooled effect size was calculated by the standardized mean difference (SMD).A total of 13 RCTs involving 514 participants by reporting 8 inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, -6, -8, -10, -15, C-reactive protein (CRP) and interferon-γ (IFN-γ) and 5 neuroprotective factors (brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), irisin] were included. The meta-analysis showed that PA had positive effects on decreasing TNF-α (SMD = - 0.32, 95% CI - 0.58 to 0.07, p = 0.01; IPA had a certain effect on inhibiting inflammatory cytokines but promoting neuroprotective factors in individuals with MCI which may provide a possible explanation for the potential molecular mechanism of PA on cognitive improvement.

Background: Oxidative stress (OS) plays an important role in the progression of many aging-related diseases. Exercises can delay this kind of progress, but aerobic exercise is the most commonly used type of training among older adults; therefore, its influence needs to be further verified.Methods: A literature search was conducted in eight electronic databases, including Cochrane, EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Date, and SinoMed from their inception to April 2020. Methodological quality was assessed using Cochrane RoB tool v2.0 for individual studies, and RevMan 5.3 software was used to perform the meta-analysis.Results: The meta-analysis included 20 studies, involving 1,170 older adults. The results showed that regular aerobic exercise could reduce blood oxidant markers, including malondialdehyde (MDA; SMD=−1.80, 95% CI −2.46 to −1.14, pp=0.02), and increase the levels of antioxidant factors, such as nitric oxide (NO; SMD=0.89, 95% CI 0.37–1.41, pp=0.001), and total antioxidant capacity (TAC; SMD=1.22, 95% CI 0.45–1.98, p=0.002), with clear statistical significance. It may also improve the levels of other OS markers, such as 8-OHdG, 8-isoPGF2, VE, and reduced glutathione/oxidized glutathione (GSH/GSSG).Conclusion: Regular aerobic exercise may have a positive effect on the OS levels of older adults by reducing some oxidant markers and increasing antioxidant marker levels.

To assess the effect of exercise interventions on subdomains of executive function (EF) in older adults with mild cognitive impairment (MCI).Nine electronic databases were comprehensively searched from their inception to February 2021. Randomized controlled trials examining the effect of exercise training on EF in MCI were included.Twenty-four eligible articles involving 2278 participants were identified. The results showed that exercise interventions had positive benefits on working memory, switching and inhibition in MCI. Subgroup analysis based on exercise prescriptions revealed that both aerobatic exercise and mind-body exercise had similar positive effect size on working memory. However, only mind-body exercise had significant effect on switching. Exercise training with moderate frequency (3-4 times/week) had larger effect size than low frequency (1-2 times/week) and only moderate frequency had positive benefits on switching. Both short (4-12 weeks), medium (13-24 weeks) and long (more than 24 weeks) exercise duration significantly ameliorate working memory and switching, however with short duration having slight larger effect sizes than medium and long.Exercise significantly improves three subdomains of EF in MCI, especially mind-body exercise. Exercise training sticking to at least 4 weeks with 3-4 times a week tends to have larger effect size.

To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 × FAD) mice.Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions.Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 × FAD mice. Aβ deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG).Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 × FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment.

How to predict the cognitive performance of Alzheimer's disease (AD) and identify the informative neuroimaging markers is essential for timely treatment and possible delay of the disease. However, incomplete labeled samples and noises in neuroimaging data pose challenges to building reliable and robust prediction models. In this paper, we present a model named Low-rank Sparse Feature Selection with Incomplete Labels (LSFSIL) for predicting cognitive performance and identifying informative neuroimaging markers with MRI data and incomplete cognitive scores.We propose a sparse matrix decomposition method to decompose the incomplete cognitive score matrix into two parts for recovering missing scores and utilizing incomplete labeled data. The former is the recovered cognitive score matrix without missing values. To make the recovered scores close to the real ones, a manifold regularizer is devised to fit the label distribution for capturing the label correlations locally. The latter is a ℓExperimental results demonstrate that LSFSIL achieves higher performance and outperforms several state-of-the-art feature selection approaches. Moreover, the neuroimaging markers selected by LSFSIL are consistent with the previous AD studies.LSFSIL is effective in informative neuroimaging marker identification for cognitive performance prediction with incomplete labeled data.

To determine the mechanism(s) involved in electroacupuncture (EA)-mediated improvements in synaptic plasticity in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R)-induced cognitive deficits.Focal cerebral ischemic stroke was induced by (MCAO/R) surgery. Rats were randomly split into 4 groups: control group (sham operation control), MCAO group, Baihui (GV 20) and Shenting (GV 24) acupoint EA group (verum acupuncture, MCAO + VA), and nonacupoint EA group (control acupuncture, MCAO + CA). EA treatment was administered for 14 consecutive days in MCAO + VA and MCAO + CA groups. Neurological assessment, behavioral performance testing, and molecular biology assays were used to evaluate the MCAO/R model, EA therapeutic effect and potential therapeutic mechanism(s) of EA.Significant amelioration of neurological deficits was found in MCAO + VA rats compared with MCAO rats (P.01). Moreover, learning and memory significantly improved in EA-treated rats compared with MCAO or MCAO + CA rats (P.05) together with an increase in the number of PSD-95EA at GV 20 and GV 24 acupoints improved cognitive deficits in cerebral ischemic rats via the JAK2/STAT3 signaling pathway and mediated synaptic plasticity in the peri-infarct hippocampal CA1 region of rats following ischemic stroke.

The default mode network (DMN) plays an important role in age-related cognitive decline. This study aims to explore the modulation effect of two mind–body interventions (Tai Chi Chuan and Baduanjin) on DMN in elderly individuals. Participants between 50 and 70 years old were recruited and randomized into a Tai Chi Chuan, Baduanjin or control group. The Wechsler Memory Scale-Chinese Revision and resting-state fMRI scans were administered at baseline and following 12 weeks of exercise. Seed-based resting-state functional connectivity (rsFC) was calculated. We found that (i) compared to the Baduanjin group, Tai Chi Chuan was significantly associated with increased rsFC between the medial prefrontal cortex (mPFC) and right putamen/caudate and (ii) compared to the control group, Tai Chi Chuan increased posterior cingulate cortex rsFC with the right putamen/caudate, while Baduanjin decreased rsFC between the mPFC and orbital prefrontal gyrus/putamen. Baseline mPFC rsFC with orbital prefrontal gyrus was negatively correlated with visual reproduction subscore. These results suggest that both Tai Chi Chuan and Baduanjin can modulate the DMN, but through different pathways. Elucidating the mechanisms underlying different mind–body interventions may shed light on the development of new methods to prevent age-related diseases as well as other disorders associated with disrupted DMN.

Numerous previous studies have suggested that physical activity or exercise may play an important role in both structural integrity of the brain and cognitive function. However, it is unclear what effect exercise has on cognitive related brain structure. The present study comprehensively reviews the effect of exercise on cognitive related brain regions of the healthy elderly by using activation likelihood estimation (ALE).Seven electronic databases were searched for randomized controlled trials published up to September 2017. The quality of the selected studies was evaluated using the Cochrane Collaboration's tool for assessing the risk of bias. GingerALE version 2.3.6 was used to perform the coordinate-based ALE meta-analysis.Nine randomized controlled trials (RCTs) with 50 distinct foci were analyzed for structural changes, containing 412 healthy older subjects. ALE showed significant regional increases in regions including the left superior temporal gyrus, left medial temporal gyrus, left inferior frontal gyrus, right medial frontal gyrus, right and left superior frontal gyrus, left cingulate gyrus, right anterior cingulate and left lentiform nucleus in subjects with the exercise intervention compared to controls. However, considering the quantity and limitations of the included studies, the conclusion could not yet be drawn. Additional randomized controlled trials with rigorous designs and longer intervention periods are needed in the future.

Background To prevent and control dementia, many scholars have focused on the transition stage between normal ageing and dementia, mild cognitive impairment (MCI) which is a key interventional target for dementia. Studies have shown that non-invasive brain stimulation (NIBS) is beneficial to improve cognitive function of MCI patients. However, whether NIBS is conducive to the protection of cognitive ability in MCI patients remains unknown due to limited evidence. The aim of the study was to systematically evaluate the modulation effect of NIBS on cognitive function (global cognitive ability and specific domains of cognition) in patients with MCI. Results A total of 11 RCTs comprising a total of 367 MCI participants. Meta-analysis showed that NIBS can significantly improve global cognition (n = 271, SMD = 0.94, 95% CI 0.47–1.41, p

To evaluate the effect of tai chi exercise on cardiac and static lung function for older community-dwelling adults at risk of ischemic stroke. A total of 170 older community-dwelling adults (aged 55–75 years old) at risk of ischemic stroke were allocated to either tai chi training group (85 cases, five 60-min sessions of tai chi training per week for 12 weeks) or control group (85 cases, usual pbysical activity for 12 weeks) using a computer-generated randomization. The echocardiographic parameters of cardiac structure, cardiac function and static lung function were measured at baseline, after 12 weeks of intervention and additional 12-week follow-up period by a blinded professional staffmember using a color Doppler ultrasound imaging device or a cardiopulmonary function instrument. The t test and linear mixed model based on the intentionto-treat analysis principle was used to calculate the effect. The adverse effect was observed. Most of echocardiographic parameters on the cardiac structure, cardiac function and static lung function between the tai chi group and control group did not have a significant difference either post 12-week intervention or additional 12-week follow-up period. Only three parameters involving in right ventricular diameter (P=0.024), main pulmonary artery diameter (P=0.002) and vital capacity maximum (P=0.036) were beneficial to be improved in the tai chi group compared to the control group by the analysis of mixed linear model. No adverse effects were found during the intervention period. The 12-week tai chi exercise did not have an obvious beneficial effect on cardiac structure, cardiac function and static lung function in older community-dwelling adults at risk of ischemic stroke. The study with a longer duration of intervention should be necessary. (Trial registration No. ChiCTR-TRC-13003601)

Processing speed is an important construct in understanding cognition. This study was aimed to control task specificity for understanding the neural mechanisms underlying cognitive processing speed. Forty young adult subjects performed attention tasks of two modalities (auditory and visual) and two levels of task rules (compatible and incompatible). Block-design fMRI captured BOLD signals during the tasks. Thirteen regions of interest were defined with reference to publicly available activation maps for processing speed tasks. Cognitive speed was derived from task reaction times, which yielded six sets of connectivity measures. Mixed-effect LASSO regression revealed six significant paths suggestive of a cerebello-frontal network predicting the cognitive speed. Among them, three are long range (two fronto-cerebellar, one cerebello-frontal), and three are short range (fronto-frontal, cerebello-cerebellar, and cerebello-thalamic). The long-range connections are likely to relate to cognitive control, and the short-range connections relate to rule-based stimulus-response processes. The revealed neural network suggests that automaticity, acting on the task rules and interplaying with effortful top-down attentional control, accounts for cognitive speed.

Background: Minimally invasive diagnostic biomarkers of neurodegenerative diseases such as Alzheimer’s disease (AD) facilitate patient selection and cognitive progressive decline monitoring. However, the diagnostic value of circulating microRNAs (miRNAs) for early cognitive impairment and progression to dementia is currently under debate. Thus, this study aimed to assess the diagnostic performance of circulating, cerebrospinal fluid (CSF) and exosomal miRNAs in the detection of clinical cognitive impairment in mild cognitive impairment (MCI), AD, and MCI-AD. Methods: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journals Database (CQVIP), and Chinese Medicine Premier (Wanfang) to identify potentially eligible studies related to noncoding RNAs and cognitive dysfunction biomarkers published before November 2018. The quality assessment of the studies was performed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Meta-analysis of the literature data was performed using Stata/MP 14.0 software. The corresponding effects models were selected to calculate the summary sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and diagnostic odds ratio (DOR) and to plot the summary receiver operating characteristic curves (SROCs) and calculate the areas under the curves (AUCs). Results: A total of 18 studies involving 729 patients with AD, 283 patients with MCI, and 15 patients with MCI-AD were pooled. The results revealed that the sensitivity and specificity of miRNAs in the diagnosis of AD were 0.78 and 0.79, respectively, and the area under the summary receiver operating characteristic curve (AUSROC) was 0.90. The sensitivity and specificity of miRNAs in the diagnosis of MCI were 0.89 and 0.85, respectively, and the AUSROC was 0.94. The sensitivity and specificity of microRNAs in the diagnosis of MCI-AD were 0.87 and 0.84, respectively, and the AUSROC was 0.92. Conclusion: Our study found that miRNAs have certain diagnostic value for cognitive impairment, with high sensitivity and specificity, especially in diagnostics with multiple miRNAs and serum-based miRNA assays.

BACKGROUND For rehabilitation training systems, it is essential to automatically record and recognize exercises, especially when more than one type of exercise is performed without a predefined sequence. Most motion recognition methods are based on feature engineering and machine learning algorithms. Time-domain and frequency-domain features are extracted from original time series data collected by sensor nodes. For high-dimensional data, feature selection plays an important role in improving the performance of motion recognition. Existing feature selection methods can be categorized into filter and wrapper methods. Wrapper methods usually achieve better performance than filter methods; however, in most cases, they are computationally intensive, and the feature subset obtained is usually optimized only for the specific learning algorithm. OBJECTIVE This study aimed to provide a feature selection method for motion recognition of upper-limb exercises and improve the recognition performance. METHODS Motion data from 5 types of upper-limb exercises performed by 21 participants were collected by a customized inertial measurement unit (IMU) node. A total of 60 time-domain and frequency-domain features were extracted from the original sensor data. A hybrid feature selection method by combining filter and wrapper methods (FESCOM) was proposed to eliminate irrelevant features for motion recognition of upper-limb exercises. In the filter stage, candidate features were first selected from the original feature set according to the significance for motion recognition. In the wrapper stage, k-nearest neighbors (kNN), Naïve Bayes (NB), and random forest (RF) were evaluated as the wrapping components to further refine the features from the candidate feature set. The performance of the proposed FESCOM method was verified using experiments on motion recognition of upper-limb exercises and compared with the traditional wrapper method. RESULTS Using kNN, NB, and RF as the wrapping components, the classification error rates of the proposed FESCOM method were 1.7%, 8.9%, and 7.4%, respectively, and the feature selection time in each iteration was 13 seconds, 71 seconds, and 541 seconds, respectively. CONCLUSIONS The experimental results demonstrated that, in the case of 5 motion types performed by 21 healthy participants, the proposed FESCOM method using kNN and NB as the wrapping components achieved better recognition performance than the traditional wrapper method. The FESCOM method dramatically reduces the search time in the feature selection process. The results also demonstrated that the optimal number of features depends on the classifier. This approach serves to improve feature selection and classification algorithm selection for upper-limb motion recognition based on wearable sensor data, which can be extended to motion recognition of more motion types and participants.

Background The aim of this study was to investigate the central mechanism underlying the putative beneficial effects of electroacupuncture (EA) on learning and memory ability of rats with ischemic stroke-induced cognitive deficits by resting-state functional magnetic resonance imaging (fMRI). Methods A rat model of middle cerebral artery occlusion (MCAO)-induced cognitive deficit (MICD) was established. Rats were randomly assigned into a sham-operated control group (SC group, n = 12), untreated MICD model group (MICD group, n = 12), and MICD group receiving EA treatment at GV20 and GV24 (MICD + EA group, n = 12). Results Compared to the MICD group, rats in the MICD + EA group receiving EA at GV20 and GV24 exhibited significantly shortened escape latency times and crossed the position of the platform a significantly increased number of times during the Morris water maze test on the 14th day after EA, which suggested EA could significantly improve spatial learning and memory ability. Furthermore, compared to the MICD group, functional connectivity of the left retrosplenial cortex (RSC) with the left hippocampus, left RSC, right RSC, left cingulate gyrus, right cingulate gyrus, right tegmentum of midbrain, and right visual cortex was increased in the MICD + EA group; the MICD group showed decreased functional connectivity of the left RSC with the left hippocampus, right hippocampus, left RSC, right RSC, right amygdaloid body, left visual cortex, and right visual cortex. Conclusion These findings suggest that EA at GV20 and GV24 might improve the learning and memory ability of MICD rats by increasing the functional connectivity between the RSC and hippocampus, cingulate gyrus and midbrain, which is encouraging for the potential treatment for cognitive impairment secondary to ischemia stroke.

IntroductionCognitive frailty (CF) is a clinical manifestation characterised by the simultaneous presence of both physical frailty and cognitive impairment among older adults without dementia and has become a new target for healthy ageing. Increasing evidence shows that regular Baduanjin (a traditional Chinese mind–body exercise) training is beneficial in improving physical function and cognitive ability in the older adults. The primary aim of this trial is to observe the effect of Baduanjin on physical and cognitive functions in older adults with CF.Methods and analysisIn this prospective, outcome assessor-blind, two-arm randomised controlled trial, a total of 102 participants with CF will be recruited and randomly allocated (1:1) into the Baduanjin training or usual physical activity control group. The control group will receive health education for 30 min at least once a month. Based on health education, participants in the Baduanjin exercise group will receive a 24-week Baduanjin training with 60 min per session and 3 sessions per week, while those in the usual physical activity control group will maintain their original lifestyle. Primary outcomes (frailty index and global cognitive ability), body composition, grip force, balance, fatigue, specific cognitive domain, including memory, execution and visual spatial abilities, and life quality of secondary outcomes will be measured at baseline, and at 13 and 25 weeks after randomisation, while the structural and functional MRI will be measured at baseline and 25 weeks after randomisation. The mixed linear model will be conducted to observe the intervention effects.Ethics and disseminationThe study has been approved by the ethics committee of the second people’s hospital of Fujian province (Approval no. 2018-KL015). Results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences.Trial registration numberChiCTR1800020341; Pre-results.

Microglia are the primary cells that exert immune function in the central nervous system, and accumulating evidence suggests that microglia act as critical players in the initiation of neurodegenerative disorders, such as Alzheimer’s disease (AD). Microglia seemingly demonstrate two contradictory phenotypes in response to different microenvironmental cues, the M1 phenotype and the M2 phenotype, which are detrimental and beneficial to pathogenesis, respectively. Inhibiting the M1 phenotype with simultaneous promoting the M2 phenotype has been suggested as a potential therapeutic approach for cure AD. In this study, we demonstrated that electroacupuncture at the Shenting and Baihui acupoints for 16 weeks could improve learning and memory in the Morris water maze test and reduce amyloid β-protein in the parietal association cortex and entorhinal cortex in mice with mild and moderate AD. Besides, electroacupuncture at the Shenting and Baihui acupoints not only suppressed M1 marker (iNOS/IL-1β) expression but also increased the M2 marker (CD206/Arg1) expression in those regions. We propose that electroacupuncture at the Shenting and Baihui acupoints could regulate microglial polarization and decrease Aβ plaques to improve learning and memory in mild AD mice.

Vascular cognitive impairment no dementia (VCIND) is likely to develop into vascular dementia (VD) without intervention. The clinical efficacy of electroacupuncture (EA) for VCIND has been previously demonstrated. However, the neuroimaging mechanism of EA for VCIND has not been elucidated clearly. This trial is designed to provide solid evidence for the efficacy and neuroimaging mechanism of EA treatment for patients with VCIND. This ongoing study is an assessor-blind, parallel-group, randomized controlled trial. 140 eligible subjects will be recruited from the General Hospital of Ningxia Medical University and randomized into either the electroacupuncture (EA) group or the control group (CG). All subjects will receive basic treatment, and participants in the CG will receive health education performed weekly. Except for basic treatment and health education, participants in the EA group will receive treatment 5 times per week for a total of 40 sessions over 8 weeks. The primary outcome in this study is Montreal Cognitive Assessment (MoCA), and the secondary outcomes are Auditory Verbal Learning Test (AVLT), Stroop color-naming condition (STROOP), Rey–Osterrieth Complex Graphics Testing, and resting-state functional magnetic resonance imaging (rs-fMRI). All of the outcome measures will be assessed at baseline and 8 weeks of intervention. The medical abstraction of adverse events will be done at each visit. The results of this trial will demonstrate the efficacy and neuroimaging mechanism of EA treatment for VCIND, thus supporting EA treatment as an ideal choice for VCIND treatment. The trial was registered at the Chinese Clinical Trial Registry on 28 July 2018 (ChiCTR1800017398).

BACKGROUND Monitoring the functional status of poststroke patients after they transition home is significant for rehabilitation. Mobile health (mHealth) technologies may provide an opportunity to reach and follow patients post discharge. However, the feasibility and validity of functional assessments administered by mHealth technologies are unknown. OBJECTIVE This study aimed to evaluate the feasibility, validity, and reliability of functional assessments administered through the videoconference function of a mobile phone–based app compared with administration through the telephone function in poststroke patients after rehabilitation hospitalization. METHODS A randomized controlled trial was conducted in a rehabilitation hospital in Southeast China. Participants were randomly assigned to either a videoconference follow-up (n=60) or a telephone follow-up (n=60) group. We measured the functional status of participants in each group at 2-week and 3-month follow-up periods. Half the participants in each group were followed by face-to-face home visit assessments as the gold standard. Validity was assessed by comparing any score differences between videoconference follow-up and home visit assessments, as well as telephone follow-up and home visit assessments. Reliability was assessed by computing agreements between videoconference follow-up and home visit assessments, as well as telephone follow-up and home visit assessments. Feasibility was evaluated by the levels of completion, satisfaction, comfort, and confidence in the 2 groups. RESULTS Scores obtained from the videoconference follow-up were similar to those of the home visit assessment. However, most scores collected from telephone administration were higher than those of the home visit assessment. The agreement between videoconference follow-up and home visit assessments was higher than that between telephone follow-up and home visit assessments at all follow-up periods. In the telephone follow-up group, completion rates were 95% and 82% at 2-week and 3-month follow-up points, respectively. In the videoconference follow-up group, completion rates were 95% and 80% at 2-week and 3-month follow-up points, respectively. There were no differences in the completion rates between the 2 groups at all follow-up periods (X21=1.6, P=.21 for 2-week follow-up; X21=1.9, P=.17 for 3-month follow-up). Patients in the videoconference follow-up group perceived higher confidence than those in the telephone follow-up group at both 2-week and 3-month follow-up periods (X23=6.7, P=.04 for 2-week follow-up; X23=8.0, P=.04 for 3-month follow-up). The videoconference follow-up group demonstrated higher satisfaction than the telephone follow-up group at 3-month follow-up (X23=13.9; P=.03). CONCLUSIONS The videoconference follow-up assessment of functional status demonstrates higher validity and reliability, as well as higher confidence and satisfaction perceived by patients, than the telephone assessment. The videoconference assessment provides an efficient means of assessing functional outcomes of patients after hospital discharge. This method provides a novel solution for clinical trials requiring longitudinal assessments. CLINICALTRIAL chictr.org.cn: ChiCTR1900027626; http://www.chictr.org.cn/edit.aspx?pid=44831&htm=4.

Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area. Our real-time live cell imaging, immunostaining and patch clamp studies showed that cofilin rod formation in neurons led to dendritic mitochondrial transportation failure, as well as impairment of synaptic structure and functions. Overexpression of LIM kinase or activation of its upstream regulator Rho, suppressed ischemia-induced cofilin rod formation and showed protective effect on synaptic function and structure impairment in both cultured neurons and MCAO-R rat model. In summary, our results demonstrate a novel mechanism of ischemic stroke-induced neuron injury in peri-infarct area and provide a potential target for the protection of neuronal structure and function against brain ischemia insult.

The primary objective of this review article was to summarize comprehensive information related to the neuropharmacological activity, mechanisms of action, toxicity, and safety of salidroside in medicine. A number of studies have revealed that salidroside exhibits neuroprotective activities, including anti-Alzheimer’s disease, anti-Parkinson’s disease, anti-Huntington’s disease, anti-stroke, anti-depressive effects, and anti-traumatic brain injury; it is also useful for improving cognitive function, treating addiction, and preventing epilepsy. The mechanisms underlying the potential protective effects of salidroside involvement are the regulation of oxidative stress response, inflammation, apoptosis, hypothalamus-pituitary-adrenal axis, neurotransmission, neural regeneration, and the cholinergic system. Being free of side effects makes salidroside potentially attractive as a candidate drug for the treatment of neurological disorders. It is evident from the available published literature that salidroside has potential use as a beneficial therapeutic medicine with high efficacy and low toxicity to the central nervous system. However, the definite target protein molecules remain unclear, and clinical trials regarding this are currently insufficient; thus, guidance for further research on the molecular mechanisms and clinical applications of salidroside is urgent.

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction (GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurological function was assessed immediately after reperfusion using Longa's 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2'-deoxyuridine (BrdU) as well as expression of the neural precursor marker doublecortin (DCX), the astrocyte marker glial fibrillary acidic protein (GFAP) and the axon regeneration marker growth associated protein-43 (GAP-43). GLGZD substantially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and increasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Our brain during distinct developmental phases may show differential responses to perceived psychological stress, yet existing research specifically examining neurodevelopmental changes in stress processing is scarce. To fill in this research gap, this functional magnetic resonance imaging (fMRI) study examined the relationship between perceived stress and resting-state neural connectivity patterns among 67 healthy volunteers belonging to three age groups (adolescents, young adults and adults), who were supposed to be at separate neurodevelopmental phases and exhibit different affect regulatory processes in the brain. While the groups showed no significant difference in self-reported general perceived stress levels, the functional connectivity between amygdala and ventromedial prefrontal cortex (vmPFC) was positively and negatively correlated with perceived stress in adolescents and young adults respectively, while no significant correlations were observed in adults. Furthermore, among adolescents, the causal functional interaction between amygdala and vmPFC exhibited bottom-up connectivity, and that between amygdala and subgenual anterior cingulate cortex exhibited top-down connectivity, both of which changed to bilateral directions, i.e. both bottom-up and top-down connections, in both young adults and adults, supporting the notion that the amygdala and prefrontal cortical circuitries undergo functional reorganizations during brain development. These novel findings have important clinical implications in treating stress-related affective disorders in young individuals., Highlights • Age moderates the relationship between prefrontal-amygdala circuitry and perceived stress. • The VMPFC-amygdala connectivity were distinct in different age groups. • The VMPFC-amygdala connectivity was positively related to stress in adolescents. • The VMPFC-amygdala connectivity was negatively related to stress in young adults. • The Ventral PFC-amygdala connectivity was bi-directional in adults.

Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats. GLGZD contains Trichosanthin and various small molecular that they are the potential active ingredients directed against NR2A, NR2B, FKBP12 and Calnodulin target proteins/enzyme have been screened by computer simulation. “Multicomponent systems” is capable to create pharmacological superposition effects. The Chinese medicine compound prescriptions could be considered as promising sources of candidates for discovery new agents.

Background For rehabilitation training systems, it is essential to automatically record and recognize exercises, especially when more than one type of exercise is performed without a predefined sequence. Most motion recognition methods are based on feature engineering and machine learning algorithms. Time-domain and frequency-domain features are extracted from original time series data collected by sensor nodes. For high-dimensional data, feature selection plays an important role in improving the performance of motion recognition. Existing feature selection methods can be categorized into filter and wrapper methods. Wrapper methods usually achieve better performance than filter methods; however, in most cases, they are computationally intensive, and the feature subset obtained is usually optimized only for the specific learning algorithm. Objective This study aimed to provide a feature selection method for motion recognition of upper-limb exercises and improve the recognition performance. Methods Motion data from 5 types of upper-limb exercises performed by 21 participants were collected by a customized inertial measurement unit (IMU) node. A total of 60 time-domain and frequency-domain features were extracted from the original sensor data. A hybrid feature selection method by combining filter and wrapper methods (FESCOM) was proposed to eliminate irrelevant features for motion recognition of upper-limb exercises. In the filter stage, candidate features were first selected from the original feature set according to the significance for motion recognition. In the wrapper stage, k-nearest neighbors (kNN), Naïve Bayes (NB), and random forest (RF) were evaluated as the wrapping components to further refine the features from the candidate feature set. The performance of the proposed FESCOM method was verified using experiments on motion recognition of upper-limb exercises and compared with the traditional wrapper method. Results Using kNN, NB, and RF as the wrapping components, the classification error rates of the proposed FESCOM method were 1.7%, 8.9%, and 7.4%, respectively, and the feature selection time in each iteration was 13 seconds, 71 seconds, and 541 seconds, respectively. Conclusions The experimental results demonstrated that, in the case of 5 motion types performed by 21 healthy participants, the proposed FESCOM method using kNN and NB as the wrapping components achieved better recognition performance than the traditional wrapper method. The FESCOM method dramatically reduces the search time in the feature selection process. The results also demonstrated that the optimal number of features depends on the classifier. This approach serves to improve feature selection and classification algorithm selection for upper-limb motion recognition based on wearable sensor data, which can be extended to motion recognition of more motion types and participants.

Cartilage degradation is an important in the pathogenesis of osteoarthritis (OA). Abnormal activation of the mitogen-activated protein kinase (MAPK) signaling pathway in chondrocytes promotes an inflammatory response, resulting in the release of chondral matrix-degrading enzymes that accelerate the degradation of cartilage. As a non-pharmaceutical and non-invasive physical therapy regimen, warm sparse-dense wave (WSDW) has been successfully used for the treatment of OA. However, it remains unclear whether WSDW inhibits cartilage degradation in OA through the MAPK signaling pathway. The present study investigated the effects of WSDW on papain-induced OA in rat knee joints. Papain-induced OA was established in rats, which were subsequently divided into a model group and three experimental groups that received a WSDW with the following ratios: WSDW=1:1, WSDW=1:2 and WSDW=2:1. After 12 weeks of treatment, cartilage degradation was evaluated by Mankin scoring of paraffin-embedded sections stained with hematoxylin and eosin. The changes in cartilage structure were observed by transmission electron microscopy, and the expressions of RAS, extracellular signal-regulated kinase (ERK), p38 and p53 were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis. WSDW was demonstrated to improve the arrangement of collagen fibers, inhibit the tidemark replication and delay cartilage degradation in papain-induced OA. The expressions of RAS, ERK, p38 and p53 in the WSDW (1:2) and (2:1) groups were significantly decreased when compared with the model group (P