Motor imagery therapy improved upper limb motor function in stroke patients with hemiplegia by increasing functional connectivity of sensorimotor and cognitive networks.

Background: Motor imagery therapy (MIT) showed positive effects on upper limbs motor function. However, the mechanism by which MIT improves upper limb motor function is not fully understood. Therefore, our purpose was to investigate the changes in functional connectivity (FC) within and outside the sensorimotor network (SMN) induced by MIT associated with improvement in upper limb motor function in stroke patients. Methods: A total of 26 hemiplegic stroke patients were randomly divided into MIT (n = 13) and control (n = 13) groups. Fugl-Meyer Assessment Upper Extremity Scale (FMA-UL), Modified Barthel Index (MBI) and resting-state functional magnetic resonance imaging (rs-fMRI) were evaluated in the two groups before treatment and 4 weeks after treatment. The efficacy of MIT on motor function improvement in stroke patients with hemiplegia was evaluated by comparing the FMA-UL and MBI scores before and after treatment in the two groups. Furthermore, the FC within the SMN and between the SMN and the whole brain was measured and compared before and after different treatment methods in stroke patients. The correlation analysis between the improvement of upper limbs motor function and changes in FC within the SMN and between the SMN and the whole brain was examined. Results: The FCs between ipsilesional primary motor cortex (M1.I) and contralateral supplementary motor area (SMA.C), M1.I and ipsilesional SMA (SMA.I), and SMA.C and contralateral dorsolateral premotor cortex (DLPM.C) significantly increased in the control group but decreased in the MIT group; while the FC between SMA.C and contralateral primary somatosensory cortex (S1.C) significantly increased in the control group but showed no significant difference in the MIT group. The FCs between M1.I and the ipsilesional hippocampal gyrus and ipsilesional middle frontal gyrus significantly decreased in the control group but increased in the MIT group; while the FC in the contralateral anterior cingulate cortex significantly increased in the MIT group but there was no significant difference in the control group. The results of the correlation analysis showed that the differences in abnormal intra-FCs within the SMN negatively correlated with the differences in FMA and MBI, and the difference in abnormal inter-FCs of the SMN positively correlated with the differences in FMA and MBI. Conclusions: MIT can improve upper limb motor function and daily activities of stroke patients, and the improvement effect of conventional rehabilitation therapy (CRT) combined with MIT is significantly higher than that of CRT alone. CRT may improve the upper limb motor function of stroke patients with hemiplegia mainly through the functional reorganization between SMN, while MIT may mainly increase the interaction between SMN and other brain networks.

Psychodynamic-based virtual reality cognitive training system with personalized emotional arousal elements for mild cognitive impairment patients.

BACKGROUND AND OBJECTIVE: Mild cognitive impairment (MCI) is a serious threat to the physical health and quality of life of the elderly, as well as a heavy burden on families and society. The current computer-based rehabilitation training ignores the role of emotions in cognitive impairment rehabilitation, making it difficult to improve patient engagement and efficiency. To address this, a psychodynamics-based cognitive rehabilitation training method with personalized emotional arousal elements was proposed using virtual reality technology. METHODS: Our proposed method contains four training tasks, which cover (audiovisual memory, attention & processing, working memory, abstract & Logic, spatial pathfinding) and six positive emotional arousal elements (sensory feedback, achievement system, multiplayer interaction, score comparison, relaxation scenarios, and peaceful videos) to motivate participants to persist during cognitive training continuously and maintain a positive mental attitude toward training. The six emotional arousal elements were divided into two personalized combinations-full combination and half combination-based on the results of the pre-assessment and were dynamically distributed throughout both the training tasks and post-training. RESULTS: Fifteen participants with MCI were recruited to complete the proposed experiment and validate the effectiveness of the system. They were first asked to complete two assessments (e.g., the big five scale and the positive and negative affect scale) to investigate their personalities. Based on the results of the assessments, they were provided with a full or half combination of arousal elements in the training tasks and post-training. Finally, the acceptability of the system and task experience were assessed using questionnaires. Notably, there was a significant increase in training scores for participants who completed a six-week training period (66.7%, 33.4%, and 25.0% for attention and processing, working memory, and abstraction and logic, respectively). The results show that positive emotional arousal had a positive effect on the MCI participants. The training tasks and arousal elements can improve cognitive function and enhance the confidence and engagement of participants. There were no significant differences in cognitive domain training scores between the two groups. CONCLUSIONS: This personalized cognitive training system has the potential to serve as a convenient solution for complementary treatment of MCI.

Comparative efficacy of different noninvasive brain stimulation therapies for recovery of global cognitive function, attention, memory, and executive function after stroke: a network meta-analysis of randomized controlled trials.

Background: Which noninvasive brain stimulation (NIBS) treatment - transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) - is more beneficial for stroke patients' cognitive rehabilitation is still up for debate. Objectives: Our goal is to provide an overview of the research on the effectiveness and safety of various NIBS protocols. Design: Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs). Methods: This NMA compared any active NIBS versus sham stimulation in adult stroke survivors to enhance cognitive function, with a focus on global cognitive function (GCF), attention, memory, and executive function (EF) using the databases MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. The NMA statistical approach was built on a frequency framework. The effect size was estimated by the standardized mean difference (SMD) and a 95% confidence interval (CI). We compiled a relative ranking of the competing interventions based on their surface under the cumulative ranking curve (SUCRA). Results: NMA showed that high-frequency repeated TMS (HF-rTMS) improved GCF compared with sham stimulation (SMD = 1.95; 95% CI: 0.47-3.43), while dual-tDCS improved memory performance versus sham stimulation significantly (SMD = 6.38; 95% CI: 3.51-9.25). However, various NIBS stimulation protocols revealed no significant impact on enhancing attention, executive function, or activities of daily living. There was no significant difference between the active stimulation protocols for TMS and tDCS and sham stimulation in terms of safety. Subgroup analysis demonstrated an effect favoring activation site of the left dorsolateral prefrontal cortex (DLPFC) (SUCRA = 89.1) for enhancing GCF and bilateral DLPFC (SUCRA = 99.9) stimulation for enhancing memory performance. Conclusion: The HF-rTMS over the left DLPFC appears to be the most promising NIBS therapeutic option for improving global cognitive performance after stroke, according to a comparison of numerous NIBS protocols. Furthermore, for patients with post-stroke memory impairment, dual-tDCS over bilateral DLPFC may be more advantageous than other NIBS protocols. Both tDCS and TMS are reasonably safe. Registration: PROSPERO ID: CRD42022304865.

Hippocampal-Subregion Mechanisms of Repetitive Transcranial Magnetic Stimulation Causally Associated with Amelioration of Episodic Memory in Amnestic Mild Cognitive Impairment.

BACKGROUND: Altered hippocampal subregions (HIPsub) and their network connectivity relate to episodic memory decline in amnestic mild cognitive impairment (aMCI), which is significantly limited by over-dependence on correlational associations. OBJECTIVE: To identify whether restoration of HIPsub and its network connectivity using repetitive transcranial magnetic stimulation (rTMS) is causally linked to amelioration of episodic memory in aMCI. METHODS: In the first cohort, analysis of HIPsub grey matter (GM) and its functional connectivity was performed to identify an episodic memory-related circuit in aMCI by using a pattern classification approach. In the second cohort, this circuit was experimentally modulated with rTMS. Structural equation modeling was employed to investigate rTMS regulatory mechanism in amelioration of episodic memory. RESULTS: First, in the first cohort, this study identified HIPsub circuit pathology of episodic memory decline in aMCI patients. Second, in the second cohort, restoration of HIPc GM and its connectivity with left middle temporal gyrus (MTG.L) are causally associated with amelioration of episodic memory in aMCI after 4 weeks of rTMS. Especially important, the effects of HIPc GM changes on the improvement of episodic memory were significantly mediated by HIPc connectivity with MTG.L changes in aMCI. CONCLUSION: This study provides novel experimental evidence about a biological substrate for the treatment of the disabling episodic memory in aMCI patients. Correction of breakdown in HIPc structure and its connectivity with MTG can causally ameliorate episodic memory in aMCI.

Functional Integrity of Executive Control Network Contributed to Retained Executive Abilities in Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is considered to be a transitional state between normal aging and Alzheimer's dementia (AD). Recent studies have indicated that executive function (EF) declines during MCI. However, only a limited number of studies have investigated the neural basis of EF deficits in MCI. Herein, we investigate the changes of regional brain spontaneous activity and functional connectivity (FC) of the executive control network (ECN) between high EF and low EF groups. Methods: According to EF composite score (ADNI-EF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we divided MCI into two groups, including the MCI-highEF group and MCI-lowEF group. Resting-state functional MRI was utilized to investigate the fractional amplitude of low-frequency fluctuation (fALFF) and ECN functional connectivity across 23 healthy controls (HC), 11 MCI-highEF, and 14 MCI-lowEF participants. Moreover, a partial correlation analysis was carried out to examine the relationship between altered fALFF or connectivity of the ECN and the ADNI-EF. Results: Compared to HC, the MCI-highEF participants demonstrated increased fALFF in the left superior temporal gyrus (STG), as well as decreased fALFF in the right precentral gyrus, right postcentral gyrus, and left middle frontal gyrus (MFG). The MCI-lowEF participants demonstrated increased fALFF in the cerebellar vermis and decreased fALFF in the left MFG. Additionally, compared to HC, the MCI-highEF participants indicated no significant difference in connectivity of the ECN. Furthermore, the MCI-lowEF participants showed increased ECN FC in the left cuneus and left MFG, as well as decreased ECN functional connectivity in the right parahippocampal gyrus (PHG). Notably, the altered fALFF in the left MFG was positively correlated to ADNI-EF, while the altered fALFF in cerebellar vermis is negatively correlated with ADNI-EF across the two MCI groups and the HC group. Altered ECN functional connectivity in the right PHG is negatively correlated to ADNI-EF, while altered ECN functional connectivity in the left cuneus is negatively correlated to ADNI-EF across the three groups. Conclusions: Our current study demonstrates the presence of different patterns of regional brain spontaneous activity and ECN FC in the MCI-highEF group and MCI-lowEF group. Furthermore, the ECN FC of the MCI-highEF group was not disrupted, which may contribute to retained EF in MCI.

Disrupted Dynamic Functional Connectivity in Distinguishing Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment Based on the Triple-Network Model.

Background: Subjective cognitive decline and amnestic mild cognitive impairment (aMCI) were widely thought to be preclinical AD spectrum disorders, characterized by aberrant functional connectivity (FC) within the triple networks of the default mode network (DMN), the salience network (SN), and the executive control network (ECN). Dynamic FC (DFC) analysis can capture temporal fluctuations in brain FC during the scan, which static FC analysis cannot. The purpose of the current study was to explore the changes in dynamic FC within the triple networks of the preclinical AD spectrum and further reveal their potential diagnostic value in diagnosing preclinical AD spectrum disorders. Methods: We collected resting-state functional magnetic resonance imaging data from 44 patients with subjective cognitive decline (SCD), 49 with aMCI, and 58 healthy controls (HCs). DFC analysis based on the sliding time-window correlation method was used to analyze DFC variability within the triple networks in the three groups. Then, correlation analysis was conducted to reveal the relationship between altered DFC variability within the triple networks and a decline in cognitive function. Furthermore, logistic regression analysis was used to assess the diagnostic accuracy of altered DFC variability within the triple networks in patients with SCD and aMCI. Results: Compared with the HC group, the groups with SCD and aMCI both showed altered DFC variability within the triple networks. DFC variability in the right middle temporal gyrus and left inferior frontal gyrus (IFG) within the ECN were significantly different between patients with SCD and aMCI. Moreover, the altered DFC variability in the left IFG within the ECN was obviously associated with a decline in episodic memory and executive function. The logistic regression analysis showed that multivariable analysis had high sensitivity and specificity for diagnosing SCD and aMCI. Conclusions: Subjective cognitive decline and aMCI showed varying degrees of change in DFC variability within the triple networks and altered DFC variability within the ECN involved episodic memory and executive function. More importantly, altered DFC variability and the triple-network model proved to be important biomarkers for diagnosing and identifying patients with preclinical AD spectrum disorders.

Altered Functional Connectivity of the Basal Nucleus of Meynert in Subjective Cognitive Impairment, Early Mild Cognitive Impairment, and Late Mild Cognitive Impairment.

Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI). Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity. Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.

Structural and Functional Disruption of Salience Network in Distinguishing Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

Salience network (SN), playing a vital role in advanced cognitive function, is regarded to be impaired in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI). The purpose of the study was to explore the importance of structural and functional features of SN in the diagnosis of SCD and aMCI. Structural and resting-state functional magnetic resonance imaging were collected from SCD, aMCI, and healthy control (HC). Cortex thickness, gray matter (GM) volume, spontaneous brain activity, functional connectivity (FC) within SN, and its relationship with cognitive function were analyzed. Moreover, the receiver operating characteristic analysis was performed to assess diagnostic efficacy of altered indictors for SCD and aMCI. Compared to HC, both SCD and aMCI showed decreased GM volume, decreased spontaneous brain activity, and increased FC within SN, while aMCI showed additional decreased cortex thickness. Furthermore, the altered FC in SCD and aMCI was significantly correlated with cognitive function. Particularly, the best-fitting classification models of SCD and aMCI were based on the combined multiple indicators. In conclusion, structure and function of SN were disrupted in SCD and aMCI, which involved in cognitive decline. The combined multiple indicators of SN provided powerful biomarkers for the diagnosis of SCD and aMCI.

Altered Frequency-Dependent Brain Activation and White Matter Integrity Associated With Cognition in Characterizing Preclinical Alzheimer's Disease Stages.

BACKGROUND: Subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer's disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration. METHODS: We analyzed ALFF under slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline. RESULTS: For ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients. CONCLUSIONS: SCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.

Altered Insular Subregional Connectivity Associated With Cognitions for Distinguishing the Spectrum of Pre-clinical Alzheimer's Disease.

Background: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are regarded as part of the pre-clinical Alzheimer's disease (AD) spectrum. The insular subregional networks are thought to have diverse intrinsic connectivity patterns that are involved in cognitive and emotional processing. We set out to investigate convergent and divergent altered connectivity patterns of the insular subregions across the spectrum of pre-clinical AD and evaluated how well these patterns can differentiate the pre-clinical AD spectrum. Method: Functional connectivity (FC) analyses in insular subnetworks were carried out among 38 patients with SCD, 56 patients with aMCI, and 55 normal controls (CNs). Logistic regression analyses were used to construct models for aMCI and CN, as well as SCD and CN classification. Finally, we conducted correlation analyses to measure the relationship between FCs of altered insular subnetworks and cognition. Results: Patients with SCD presented with reduced FC in the bilateral cerebellum posterior lobe and increased FC in the medial frontal gyrus and the middle temporal gyrus. On the other hand, patients with aMCI largely presented with decreased FC in the bilateral inferior parietal lobule, the cerebellum posterior lobe, and the anterior cingulate cortex, as well as increased FC in the medial and inferior frontal gyrus, and the middle and superior temporal gyrus. Logistic regression analyses indicated that a model composed of FCs among altered insular subnetworks in patients with SCD was able to appropriately classify 83.9% of patients with SCD and CN, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.876, 81.6% sensitivity, and 81.8% specificity. A model consisting of altered insular subnetwork FCs in patients with aMCI was able to appropriately classify 86.5% of the patients with aMCI and CNs, with an AUC of 0.887, 80.4% sensitivity, and 83.6% specificity. Furthermore, some of the FCs among altered insular subnetworks were significantly correlated with episodic memory and executive function. Conclusions: Patients with SCD and aMCI are likely to share similar convergent and divergent altered intrinsic FC patterns of insular subnetworks as the pre-clinical AD spectrum, and presented with abnormalities among subnetworks. Based on these abnormalities, individuals can be correctly differentiated in the pre-clinical AD spectrum. These results suggest that alterations in insular subnetworks can be utilized as a potential biomarker to aid in conducting a clinical diagnosis of the spectrum of pre-clinical AD.

rTMS modulates precuneus-hippocampal subregion circuit in patients with subjective cognitive decline.

Hippocampal subregions (HIPsub) and their network connectivities are generally aberrant in patients with subjective cognitive decline (SCD). This study aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS) could ameliorate HIPsub network connectivity by modulating one node of HIPsub network in SCD. In the first cohort, the functional connectivity (FC) of three HIPsub (i.e., hippocampal emotional, cognitive, and perceptual regions: HIPe, HIPc, and HIPp) were analyzed so as to identify alterations in HIPsub connectivity associated with SCD. Afterwards, a support vector machine (SVM) approach was applied using the alterations in order to evaluate to what extent we could distinguish SCD from healthy controls (CN). In the second cohort, a 2-week rTMS course of 5-day, once-daily, was used to activate the altered HIPsub network connectivity in a sham-controlled design. SCD subjects exhibited distinct patterns alterations of HIPsub network connectivity compared to CN in the first cohort. SVM classifier indicated that the abnormalities had a high power to discriminate SCD from CN, with 92.9% area under the receiver operating characteristic curve (AUC), 86.0% accuracy, 83.8% sensitivity and 89.1% specificity. In the second cohort, changes of HIPc connectivity with the left parahippocampal gyrus and HIPp connectivity with the left middle temporal gyrus demonstrated an amelioration of episodic memory in SCD after rTMS. In addition, SCD exhibited improved episodic memory after the rTMS course. rTMS therapy could improve the posterior hippocampus connectivity by modulating the precuneus in SCD. Simultaneous correction of the breakdown in HIPc and HIPp could ameliorate episodic memory in SCD. Thus, these findings suggested that rTMS manipulation of precuneus-hippocampal circuit might prevent disease progression by improving memory as the earliest at-risk state of Alzheimer's disease in clinical trials and in practice.

Disrupted Patterns of Rich-Club and Diverse-Club Organizations in Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment.

BACKGROUND: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) were considered to be a continuum of Alzheimer's disease (AD) spectrum. The abnormal topological architecture and rich-club organization in the brain functional network can reveal the pathology of the AD spectrum. However, few studies have explored the disrupted patterns of diverse club organizations and the combination of rich- and diverse-club organizations in SCD and aMCI. METHODS: We collected resting-state functional magnetic resonance imaging data of 19 SCDs, 29 aMCIs, and 28 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative. Graph theory analysis was used to analyze the network metrics and rich- and diverse-club organizations simultaneously. RESULTS: Compared with HC, the aMCI group showed altered small-world and network efficiency, whereas the SCD group remained relatively stable. The aMCI group showed reduced rich-club connectivity compared with the HC. In addition, the aMCI group showed significantly increased feeder connectivity and decreased local connectivity of the diverse club compared with the SCD group. The overlapping nodes of the rich club and diverse club showed a significant difference in nodal efficiency and shortest path length (L p) between groups. Notably, the L p values of overlapping nodes in the SCD and aMCI groups were significantly associated with episodic memory. CONCLUSION: The present study demonstrates that the network properties of SCD and aMCI have varying degrees of damage. The combination of the rich club and the diverse club can provide a novel insight into the pathological mechanism of the AD spectrum. The altered patterns in overlapping nodes might be potential biomarkers in the diagnosis of the AD spectrum.

[ß-caryophyllene alleviates cerebral ischemia/ reperfusion injury in mice by activating autophagy].

Cerebral ischemia-reperfusion(I/R) injury is an important cause of acute ischemic stroke. Timely elimination of damaged proteins and organelles by regulating autophagy during cerebral ischemia-reperfusion plays an important role in relieving brain damage. In order to investigate whether ß-caryophyllene(BCP) could protect neurons from cerebral I/R injury by regulating auto-phagy, C57 BL/6 J male mice were randomly divided into sham operation group, model group, and drug-administered group. After intra-gastric administration was given for 5 days, the middle cerebral artery occlusion(MCAO) model was established by suture method. Twenty four hours after surgery, the infarct volume and neurological function were assessed; the pathological changes of cortical tissue were observed by HE staining; Western blot was used to detect the expression of autophagy-related proteins beclin1, p62, LC3 B and apoptosis-related protein Bcl-2; immunofluorescence was used to observe the expression of LC3 B in the ischemic cortex. The autophagy of cortical tissue in the ischemic area was observed by transmission electron microscopy. The experimental results showed that as compared with the model group, the BCP pretreatment significantly reduced the neurological deficit, decreased the percentage of cerebral infarction volume, reduced the death of brain tissue cells in the ischemic area, up-regulated the expression of beclin1, LC3 B and Bcl-2 protein, down-regulated p62 protein expression, and significantly increased the number of autophagosomes in the cortical tissue of the ischemic area. It was finally determined that BCP could protect neurons from cerebral ischemia-reperfusion injury by activating autophagy.

Altered Rich-Club Organization and Regional Topology Are Associated With Cognitive Decline in Patients With Frontal and Temporal Gliomas.

OBJECTIVES: Gliomas are widely considered to be related to the altered topological organization of functional networks before operations. Tumors are usually thought to cause multimodal cognitive impairments. The structure is thought to form the basics of function, and the aim of this study was to reveal the rich-club organization and topological patterns of white matter (WM) structural networks associated with cognitive impairments in patients with frontal and temporal gliomas. METHODS: Graph theory approaches were utilized to reveal the global and regional topological organization and rich-club organization of WM structural networks of 14 controls (CN), 13 frontal tumors (FTumor), and 18 temporal tumors (TTumor). Linear regression was used to assess the relationship between cognitive performances and altered topological parameters. RESULTS: When compared with CN, both FTumor and TTumor showed no alterations in small-world properties and global network efficiency, but instead showed altered local network efficiency. Second, FTumor and TTumor patients showed similar deficits in the nodal shortest path in the left rolandic operculum and degree centrality (DC) of the right dorsolateral and medial superior frontal gyrus (SFGmed). Third, compared to FTumor patients, TTumor patients showed a significantly higher DC in the right dorsolateral and SFGmed, a higher level of betweenness in the right SFGmed, and higher nodal efficiency in the left middle frontal gyrus and right SFGmed. Finally, rich-club organization was disrupted, with increased structural connectivity among rich-club nodes and reduced structural connectivity among peripheral nodes in FTumor and TTumor patients. Altered local efficiency in TTumor correlated with memory function, while altered local efficiency in FTumor correlated with the information processing speed. CONCLUSION: Both FTumor and TTumor presented an intact global topology and altered regional topology related to cognitive impairment and may also share the convergent and divergent regional topological organization of WM structural networks. This suggested that a compensatory mechanism plays a key role in global topology formation in both FTumor and TTumor patients, and as such, development of a structural connectome for patients with brain tumors would be an invaluable medical resource and allow clinicians to make comprehensive preoperative planning.

Distinct Disruptive Patterns of Default Mode Subnetwork Connectivity Across the Spectrum of Preclinical Alzheimer's Disease.

Background: The early progression continuum of Alzheimer's disease (AD) has been considered to advance through subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI). Altered functional connectivity (FC) in the default mode network (DMN) is regarded as a hallmark of AD. Furthermore, the DMN can be divided into two subnetworks, the anterior and posterior subnetworks. However, little is known about distinct disruptive patterns in the subsystems of the DMN across the preclinical AD spectrum. This study investigated the connectivity patterns of anterior DMN (aDMN) and posterior DMN (pDMN) across the preclinical AD spectrum. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in the DMN subnetworks in 20 healthy controls (HC), eight SCD, 11 naMCI, and 28 aMCI patients. Moreover, a correlation analysis was used to examine associations between the altered connectivity of the DMN subnetworks and the neurocognitive performance. Results: Compared to the HC, SCD patients showed increased FC in the bilateral superior frontal gyrus (SFG), naMCI patients showed increased FC in the left inferior parietal lobule (IPL), and aMCI patients showed increased FC in the bilateral IPL in the aDMN; while SCD patients showed decreased FC in the precuneus, naMCI patients showed increased FC in the left middle temporal gyrus (MTG), and aMCI patients also showed increased FC in the right middle frontal gyrus (MFG) in the pDMN. Notably, the FC between the ventromedial prefrontal cortex (vmPFC) and the left MFG and the IPL in the aDMN was associated with episodic memory in the SCD and aMCI groups. Interestingly, the FC between the posterior cingulated cortex (PCC) and several regions in the pDMN was associated with other cognitive functions in the SCD and naMCI groups. Conclusions: This study demonstrates that the three preclinical stages of AD exhibit distinct FC alternations in the DMN subnetworks. Furthermore, the patient group data showed that the altered FC involves cognitive function. These findings can provide novel insights for tailored clinical intervention across the preclinical AD spectrum.

The Effectiveness of Action Observation Therapy Based on Mirror Neuron Theory in Chinese Patients with Apraxia of Speech after Stroke.

OBJECTIVE: The present study aimed to evaluate the efficacy of action observation therapy (AOT) on apraxia of speech (AOS) in patients after stroke. MATERIALS AND METHODS: Forty-two patients diagnosed with AOS after stroke were randomly divided into an experimental group (n = 21) and a control group (n = 21). Both groups received 30 min of conventional language therapy twice daily, 5 days a week for 4 weeks. The patients in the experimental group additionally received 20 min of AOT before 10 min language therapy each day. The speech function and aphasia severity of the 2 groups were assessed using the speech apraxia assessment method of the China Rehabilitation Research Center, Western Aphasia Battery (WAB), and the Boston Diagnostic Aphasia Examination before and after treatment. RESULTS: AOS and WAB scores increased significantly after treatment in both groups (p < 0.05). AOS and WAB scores exhibited significant differences between the experimental group and the control group after training (p < 0.05). The response rate in the experimental group was significantly higher than that in the control group (p < 0.05). CONCLUSION: AOT based on mirror neuron theory may improve language function in patients with AOS after stroke.

[Study on genetic polymorphism of Platycodon grandiflorum based on barcoding of ITS2].

OBJECTIVE: ITS2 of DNA barcoding was used to study genetic polymorphism of Platycodon grandiflorum. METHOD: Total genomic DNA was isolated from P. grandiflorum. PCR was used to amplified the region of internal transcribed spacer 2 (ITS2), and PCR products were sequenced. The sequences of ITS2 were analyzed and compared by Clustal. The intraspecies genetic distance was calculated based on Kimura 2-parameter model by using MEGA 5.05. The ITS2 sequence of Codonopsis pilosula was used as the outreach value for plants of the genus, and the phylogenic tree used constructed by Neighbor-Joining (NJ) method. RESULT: The K2-P's genetic distance of all samples were ranged from 0 to 0.930. The K2-P's genetic distance of samples at the same area were ranged from 0 to 0.178. The K2-P's genetic distance of samples at different areas were ranged from 0.735 to 0.930. The analytical result showed that the degree of genetic variation were heavy in intraspecies of P. grandiflorum and significantly correlated with geographical location. CONCLUSION: The DNA barcoding of ITS2 can applied to study the intraspecific genetic diversity, it provides a reference for further development of DNA barcoding technology applications.

A method for exploring adult neurogenesis in the songbird brain.

The avian brain is a valuable model for exploring adult neurogenesis. Here we use immunohistochemical methods to detect cell division and the incorporation of new neurons in the adult zebra finch brain. The nonradioactive, relatively inexpensive thymidine analog bromodeoxyuridine (BrdU) is used to label replicating DNA in dividing cells. The brain is harvested, fixed, and dehydrated before being embedded in polyethylene glycol (PEG), which results in superior histology compared to frozen specimens. After the PEG-embedded brain tissue is sectioned and mounted on slides, standard immunohistochemical procedures are used to detect both BrdU and the neuron-specific marker Hu.

Health risk factors and presenteeism: a look into employees at two enterprises in China / 中华健康管理学杂志

Objective To analyze the effects of health risk factors on presenteeism in enterprise employees.Methods A hospital in Jinan of Shandong province and a publishing enterprise in Beijing were selected as target settings of this cross-sectional study. Questionnaire survey was carried out to collect information on demographic data,health condition and presenteeism,and multiple logistic regression was used to analyze the influence of health risk factors on labor-related presenteeism.Results Insufficient physical activity was found in 42％ percent of the participants,and those with heavy-loaded pressure,overweight or obesity,high blood pressure and unhealthy diet habit accounted for 46％,41％,40％ and 34％,respectively. Proportions of employees with presenteeism varied with age ( x2 =10.1665,P =0.0377),occupation ( x2 =35.3579,P ＜ 0.05 ) and education level ( x2 =50.5377,P ＜ 0.05 ).Female employees ( P =0.0323,OR =1.728,95％ CI 1.047 to 2.850),graduates ( P ＜ 0.05,OR =6.159,95％ CI 2.510 to 15.109),overweight or obesity individuals ( P =0.0076,OR =1.673,95％ CI 1.147 to 2.44) and adults with poor self-perception of health ( P =0.0049,OR =2.284,95％ CI 1.285 to 4.060)seemed to be more likely to be presenteeism.Conclusions Overweight or obesity and poor self-perception of health may be associated with labor-related presenteeism.