Brain network hierarchy reorganization in subthreshold depression.

BACKGROUND: Hierarchy is the organizing principle of human brain network. How network hierarchy changes in subthreshold depression (StD) is unclear. The aim of this study was to investigate the altered brain network hierarchy and its clinical significance in patients with StD. METHODS: A total of 43 patients with StD and 43 healthy controls matched for age, gender and years of education participated in this study. Alterations in the hierarchy of StD brain networks were depicted by connectome gradient analysis. We assessed changes in network hierarchy by comparing gradient scores in each network in patients with StD and healthy controls. The study compared different brain subdivisions if there was a different network. Finally, we analysed the relationship between the altered gradient scores and clinical characteristics. RESULTS: Patients with StD had contracted network hierarchy and suppressed cortical range gradients. In the principal gradient, the gradient scores of default mode network were significantly reduced in patients with StD compared to controls. In the default network, the subdivisions of reduced gradient scores were mainly located in the precuneus, superior temporal gyrus, and anterior and posterior cingulate gyrus. Reduced gradient scores in the default mode network, the anterior and posterior cingulate gyrus were correlated with severity of depression. CONCLUSIONS: The network hierarchy of the StD changed and was significantly correlated with depressive symptoms and severity. These results provided new insights into further understanding of the neural mechanisms of StD.

Emerging Role of Interleukin-38 (IL-38) in the Development of Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. METHODS: In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1ß, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. RESULTS: At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1ß significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1ß among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1ß exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. CONCLUSION: IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Alterations in hippocampus-centered morphological features and function of the progression from normal cognition to mild cognitive impairment.

Mild cognitive impairment (MCI) is a significant precursor to dementia, highlighting the critical need for early identification of individuals at high risk of MCI to prevent cognitive decline. The study aimed to investigate the changes in brain structure and function before the onset of MCI. This study enrolled 19 older adults with progressive normal cognition (pNC) to MCI and 19 older adults with stable normal cognition (sNC). The gray matter (GM) volume and functional connectivity (FC) were estimated via magnetic resonance imaging during their normal cognition state 3 years prior. Additionally, spatial associations between FC maps and neurochemical profiles were examined using JuSpace. Compared to the sNC group, the pNC group showed decreased volume in the left hippocampus and left amygdala. The significantly positive correlation was observed between the GM volume of the left hippocampus and the MMSE scores after 3 years in pNC group. Besides, it showed that the pNC group had increased FC between the left hippocampus and the anterior-posterior cingulate gyrus, which was significantly correlated with the spatial distribution of dopamine D2 and noradrenaline transporter. Taken together, the study identified the abnormal brain characteristics before the onset of MCI, which might provide insight into clinical research.

Atypical characteristic changes of surface morphology and structural covariance network in developmental dyslexia.

BACKGROUND: Developmental dyslexia (DD) is a neurodevelopmental disorder that is characterized by difficulties with all aspects of information acquisition in the written word, including slow and inaccurate word recognition. The neural basis behind DD has not been fully elucidated. METHOD: The study included 22 typically developing (TD) children, 16 children with isolated spelling disorder (SpD), and 20 children with DD. The cortical thickness, folding index, and mean curvature of Broca's area, including the triangular part of the left inferior frontal gyrus (IFGtriang) and the opercular part of the left inferior frontal gyrus, were assessed to explore the differences of surface morphology among the TD, SpD, and DD groups. Furthermore, the structural covariance network (SCN) of the triangular part of the left inferior frontal gyrus was analyzed to explore the changes of structural connectivity in the SpD and DD groups. RESULTS: The DD group showed higher curvature and cortical folding of the left IFGtriang than the TD group and SpD group. In addition, compared with the TD group and the SpD group, the structural connectivity between the left IFGtriang and the left middle-frontal gyrus and the right mid-orbital frontal gyrus was increased in the DD group, and the structural connectivity between the left IFGtriang and the right precuneus and anterior cingulate was decreased in the DD group. CONCLUSION: DD had atypical structural connectivity in brain regions related to visual attention, memory and which might impact the information input and integration needed for reading and spelling.

Automatic brain extraction for rat magnetic resonance imaging data using U2-Net.

Objective.Skull stripping is a key step in the pre-processing of rodent brain magnetic resonance images (MRI). This study aimed to develop a new skull stripping method via U2-Net, a neural network model based on deep learning method, for rat brain MRI.Approach.In this study, 599 rats were enrolled and U2-Net was applied to segment MRI images of rat brain. The intercranial tissue of each rat was manually labeled. 476 rats (approximate 80%) were used for training set while 123 rats (approximate 20%) were used to test the performance of the trained U2-Net model. For evaluation, the segmentation result by the U2-Net model is compared with the manual label, and traditional segment methods. Quantitative evaluation, including Dice coefficient, Jaccard coefficient, Sensitivity, Specificity, Pixel accuracy, Hausdorff coefficient, True positive rate, False positive rate and the volumes of whole brain, were calculated to compare the segmentation results among different models.Main results.The U2-Net model was performed better than the software of RATS and BrainSuite, in which the quantitative values of training U2-Net model were 0.9907 ± 0.0016 (Dice coefficient), 0.9816 ± 0.0032 (Jaccard coefficient), 0.9912 ± 0.0020 (Sensitivity), 0.9989 ± 0.0002 (Specificity), 0.9982 ± 0.0003 (Pixel accuracy), 5.2390 ± 2.5334 (Hausdorff coefficient), 0.9902 ± 0.0025 (True positive rate), 0.0009 ± 0.0002(False positive rate) respectively.Significance.This study provides a new method that achieves reliable performance in rat brain skull stripping of MRI images, which could contribute to the processing of rat brain MRI.

Altered morphological characteristics and structural covariance connectivity associated with verbal working memory performance in ADHD children.

OBJECTIVES: Deficits in verbal working memory (VWM) observed in attention deficit hyperactivity disorder (ADHD) children can persist into adulthood. Although previous studies have identified brain regions that are activated during VWM tasks, the neural mechanisms underlying the relationship between VWM deficits remain unclear. The objective of this study was to investigate the structural covariance network connectivity and brain morphology changes that are associated with VWM performance in ADHD children. METHODS: For this study, we selected 26 ADHD children and 26 healthy control (HC) participants. Participants were instructed to perform an n-back VWM task and their accuracy and response times were subsequently recorded. This research utilised voxel-based morphometry to measure the grey matter (GM) volume and conducted structural covariance connectivity network analysis to explore the changes of brain in ADHD. RESULTS: Voxel-based morphometry analysis showed that lower GM volume in the right cerebellum lobule VI and the left parahippocampal gryus in ADHD children. Moreover, a positive correlation was found between the GM volume in the right cerebellum lobule VI and the accuracy of 2-back VWM task with verbal, small reward, and delayed feedback (VSD). Structural covariance network analysis found decreased structural connectivity between right cerebellum lobule VI and right precentral gyrus, right postcentral gyrus, left paracentral lobule, right superior parietal gyrus, and left hippocampus in ADHD children. CONCLUSIONS: The low GM volume and altered structural covariance connectivity in the right cerebellum lobule VI might potentially affect VWM performance in ADHD children. ADVANCES IN KNOWLEDGE: The innovation of this study lies in its more focused discussion on the morphological characteristics and structural covariance connectivity of VWM deficits in ADHD children, and the innovative finding of a positive correlation between grey matter volume in the right cerebellum lobule VI and accuracy in completing the 2-back VWM task with verbal instructions, small reward, and delayed feedback (VSD). This expands upon previous research by elucidating the specific brain structures involved in VWM deficits in ADHD children and highlights the potential importance of the cerebellum in this cognitive process. Overall, these innovative findings advance our understanding of the neural basis of ADHD and may have important implications for the development of targeted interventions for VWM deficits.

Effects of computerized cognitive training on structure‒function coupling and topology of multiple brain networks in people with mild cognitive impairment: a randomized controlled trial.

BACKGROUND: People with mild cognitive impairment (MCI) experience a loss of cognitive functions, whose mechanism is characterized by aberrant structure‒function (SC-FC) coupling and topological attributes of multiple networks. This study aimed to reveal the network-level SC-FC coupling and internal topological changes triggered by computerized cognitive training (CCT) to explain the therapeutic effects of this training in individuals with MCI. METHODS: In this randomized block experiment, we recruited 60 MCI individuals and randomly divided them into an 8-week multidomain CCT group and a health education control group. The neuropsychological outcome measures were the Montreal Cognitive Assessment (MoCA), Chinese Auditory Verbal Learning Test (CAVLT), Chinese Stroop Color-Word Test (SCWT), and Rey-Osterrieth Complex Figure Test (Rey CFT). The brain imaging outcome measures were SC-FC coupling and topological attributes using functional MRI and diffusion tensor imaging methods. We applied linear model analysis to assess the differences in the outcome measures and identify the correspondence between the changes in the brain networks and cognitive functions before and after the CCT. RESULTS: Fifty participants were included in the analyses after the exclusion of three dropouts and seven participants with low-quality MRI scans. Significant group × time effects were found on the changes in the MoCA, CAVLT, and Rey CFT recall scores. The changes in the SC-FC coupling values of the default mode network (DMN) and somatomotor network (SOM) were higher in the CCT group than in the control group (P(unc.) = 0.033, P(unc.) = 0.019), but opposite effects were found on the coupling values of the visual network (VIS) (P(unc.) = 0.039). Increasing clustering coefficients in the functional DMN and SOM and subtle changes in the nodal degree centrality and nodal efficiency of the right dorsal medial prefrontal cortex, posterior cingulate cortex, left parietal lobe, somatomotor area, and visual cortex were observed in the CCT group (P < 0.05, Bonferroni correction). Significant correspondences were found between global cognitive function and DMN coupling values (P(unc.) = 0.007), between immediate memory and SOM as well as FPC coupling values (P(unc.) = 0.037, P(unc.) = 0.030), between delayed memory and SOM coupling values (P(unc.) = 0.030), and between visual memory and VIS coupling values (P(unc.) = 0.007). CONCLUSIONS: Eight weeks of CCT effectively improved global cognitive and memory functions; these changes were correlated with increases in SC-FC coupling and changes in the topography of the DMN and SOM in individuals with MCI. The CCT regimen also modulated the clustering coefficient and the capacity for information transformation in functional networks; these effects appeared to underlie the cognitive improvement associated with CCT. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000034012. Registered on 21 June 2020.

Computerized Cognitive Training Enhances Episodic Memory by Down-Modulating Posterior Cingulate-Precuneus Connectivity in Older Persons With Mild Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: The neural mechanisms underlying the beneficial effects of a computerized cognitive training (CCT) program for improving episodic memory in older persons with mild cognitive impairment (MCI) remain unclear. This study aimed to use both functional and structural brain changes to elucidate the treatment effects of CCT on enhancing episodic memory. DESIGN, SETTING, AND PARTICIPANTS: Single-blinded, multicenter randomized controlled trial on 60 older adults with MCI in Fuzhou, China. INTERVENTION: Participants were randomly assigned to either an 8-week 24-hour CCT program or a health education program as the control. MEASUREMENTS: Clinical outcomes included changes in scores on the immediate and/or delayed recall subtests of the Chinese auditory verbal learning test (CAVLT) and rey complex figure test (CFT), and changes in gray matter volume and the functional connectivity of the posterior cingulate cortex (PCC) and hippocampus in the Papez circuit on magnetic resonance imaging. RESULTS: Significant group-by-time effects showed greater improvements in both immediate and delayed recall scores of CAVLT and delayed recall scores of Rey CFT in participants receiving the CCT program compared to those in the health education program. Among the CCT participants, seed-based analyses revealed decreases in functional connectivity of the PCC and hippocampus with neural substrates in the parietal and occipital regions. The decreased PCC and precuneus connectivity were found to mediate patients' improvements in immediate recall function. CONCLUSION: An 8-week CCT program was effective for improving episodic memory in older individuals with MCI. The decrease in connectivity originating from the PCC and hippocampus is suggestive of potential plastic changes in the Papez circuit, which could have alleviated the age-related compensatory mechanism. The findings of this study also shed light on expanding the content and extending the frequency and duration of the CCT program in future studies.

Effects of Tai Chi Chuan on Cognitive Function in Adults 60 Years or Older With Type 2 Diabetes and Mild Cognitive Impairment in China: A Randomized Clinical Trial.

Importance: Type 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). Objective: To 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 Participants: This 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. Interventions: Participants 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 Measures: The 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. Results: A 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 Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT04416841.

Brain functional activity of swallowing: A meta-analysis of functional magnetic resonance imaging.

BACKGROUND: Swallowing is one of the most important activities in our life and serves the dual roles of nutritional intake and eating enjoyment. OBJECTIVE: The study aimed to conduct a meta-analysis to investigate the brain activity of swallowing. METHODS: Studies of swallowing using functional magnetic resonance imaging were reviewed in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP) and Wan Fang before 30 November 2021. Two authors analysed the studies for eligibility criteria. The final inclusion of studies was decided by consensus. An activation likelihood estimation (ALE) meta-analysis of these studies was performed with GingerALE, including 16 studies. RESULTS: For swallowing, clusters with high activation likelihood were found in the bilateral insula, bilateral pre-central gyrus, bilateral post-central gyrus, left transverse temporal gyrus, right medial front gyrus, bilateral inferior frontal gyrus and bilateral cingulate gyrus. For water swallowing, clusters with high activation likelihood were found in the bilateral inferior frontal gyrus and the left pre-central gyrus. For saliva swallowing, clusters with high activation likelihood were found in the bilateral cingulate gyrus, bilateral pre-central gyrus, left post-central gyrus and left transverse gyrus. CONCLUSION: This meta-analysis reflects that swallowing is regulated by both sensory and motor cortex, and saliva swallowing activates more brain areas than water swallowing, which would promote our knowledge of swallowing and provide some direction for clinical and other research.

Ischemic stroke rehabilitation through optogenetic modulation of parvalbumin neurons in the contralateral motor cortex.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Physical exercise/sports ameliorate the internet addiction from college students during the pandemic of COVID-19 in China.

The rapid advancement of modern technology has significantly driven progress in various IT-related activities, resulting in a substantial increase in internet penetration rates, particularly among college students. The utilization of the internet has become one of the most essential tools in our modern society. However, internet addiction (IA) has emerged as a serious concern, particularly among college students, adversely affecting academic performance and having significant psychological and psychiatric implications. The aim of the current study was to determine the impact of physical exercise, gender and academic year on IA among college students. In the present study, we investigated internet usage, engagement in sports activities, and academic performance among college students from Western, Middle, and Eastern regions of Chinese universities. It's noteworthy that most of the respondents were freshmen. Our findings indicate that freshmen students were more susceptible to experiencing IA. Approximately 75% of students engaged in leisure sports activities, revealing an inverse correlation between sports activity and IA. This correlation aligns with the level of sports involvement, emphasizing the potential benefits of physical activity in mitigating IA. However, our study did not uncover any correlation between geographic location and the occurrence of IA, nor did it find differences between medical and non-medical students. Furthermore, our study revealed no significant variations in IA among students from different ethnic backgrounds. The underlying mechanism of IA is being currently determined. Our data suggest that physical exercise, gender, and academic year have a significant impact on IA among college students.

Functional Connectivity of Ipsilateral Striatum in Rats with Ischemic Stroke Increased by Electroacupuncture.

BACKGROUND: This study aimed to investigate the effects of electroacupuncture (EA) treatment at Zusanli (ST36) and Quchi (LI11) on cortico-striatal network connectivity after ischemia stroke by resting-state functional magnetic resonance imaging (fMRI). METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established. Rats were randomly assigned into a sham-operated control group (SC group, n = 8), untreated MCAO model group (MCAO group, n = 8), and MCAO group receiving EA treatment at ST36 and LI11 (MCAO + EA group, n = 8). Rats in the SC and the MCAO groups received no treatment. The MCAO + EA group was treated with EA from the 1st day to the 7th day after surgery. The behavioral tests including Zea Longa test and modified neurologic severity score (mNSS) for all rats were performed before and after treatment for MCAO + EA group. fMRI scans were performed after behavioral tests on the 7th day after surgery. RESULTS: The neurologic severity scores estimated by Zea Longa and mNSS were significantly improved in the rat ischemic stroke model of MCAO within 1 week after EA treatment at acupoints ST36 and LI11. Besides, voxel-wise analysis showed that EA could increase the functional connectivity of the left striatum with the bilateral sensory cortex, bilateral motor cortex, left retrosplenial cortex, right cerebellum, bilateral hippocampus, bilateral auditory cortex, bilateral visual cortex, left parietal cortex, left cingulate gyrus, and left superior colliculus. Further graph theory analysis showed that EA significantly decreased the characteristic path length and increased the global efficiency of the cortico-striatal network. CONCLUSIONS: EA at ST36 and LI11 could improve the cortico-striatal network to impact the brain's protective in MCAO, which is a potential treatment for ischemia stroke.

The current status and trend of the functional magnetic resonance combined with stimulation in animals.

As a non-radiative, non-invasive imaging technique, functional magnetic resonance imaging (fMRI) has excellent effects on studying the activation of blood oxygen levels and functional connectivity of the brain in human and animal models. Compared with resting-state fMRI, fMRI combined with stimulation could be used to assess the activation of specific brain regions and the connectivity of specific pathways and achieve better signal capture with a clear purpose and more significant results. Various fMRI methods and specific stimulation paradigms have been proposed to investigate brain activation in a specific state, such as electrical, mechanical, visual, olfactory, and direct brain stimulation. In this review, the studies on animal brain activation using fMRI combined with different stimulation methods were retrieved. The instruments, experimental parameters, anesthesia, and animal models in different stimulation conditions were summarized. The findings would provide a reference for studies on estimating specific brain activation using fMRI combined with stimulation.

Aberrant pattern of regional cerebral blood flow in mild cognitive impairment: A meta-analysis of arterial spin labeling magnetic resonance imaging.

In mild cognitive impairment (MCI), cognitive decline is associated with abnormal changes of cerebral blood flow (CBF). Arterial spin labeling magnetic resonance imaging (ASL-MRI) is an effective method for assessing regional cerebral blood flow (rCBF). However, the CBF estimated via ASL-MRI in MCI often differs between studies, and the consistency of CBF changes in MCI is unclear. In this study, 13 ASL-MRI studies with 495 MCI patients and 441 health controls were screened out from PubMed, Embase, Cochrane, Web of Science, Wanfang, and CNKI. An activation likelihood estimation (ALE) meta-analysis was performed to explore the brain regions with abnormal CBF in MCI. It showed that the decreased CBF in MCI was identified in the precuneus, inferior parietal lobule (IPL), superior occipital gyrus (SOG), middle temporal gyrus (MTG), and middle occipital gyrus (MOG), while the increased CBF in MCI was identified in the lentiform nucleus (LN) compared with healthy controls. The study characterized the abnormal pattern of regional CBF in MCI, which would promote our knowledge of MCI and might be used as a biomarker in clinic. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259633.

A novel rat model for cerebral venous sinus thrombosis: verification of similarity to human disease via clinical analysis and experimental validation.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical courses. Animal models properly matched to the clinical form of CVST are necessary for elucidating the pathophysiology of the disease. In this study, we aimed to establish a rat model that accurately recapitulates the clinical features of CVST in human patients. METHODS: This study consisted of a clinical analysis and animal experiments. Clinical data for two centres obtained between January 2016 and May 2021 were collected and analysed retrospectively. In addition, a Sprague-Dawley rat model of CVST was established by inserting a water-swellable rubber device into the superior sagittal sinus, following which imaging, histological, haematological, and behavioural tests were used to investigate pathophysiological changes. Principal component analysis and hierarchical clustering heatmaps were used to evaluate the similarity between the animal models and human patients. RESULTS: The imaging results revealed the possibility of vasogenic oedema in animal models. Haematological analysis indicated an inflammatory and hypercoagulable state. These findings were mostly matched with the retrospective clinical data. Pathological and serological tests further revealed brain parenchymal damage related to CVST in animal models. CONCLUSIONS: We successfully established a stable and reproducible rat model of CVST. The high similarity between clinical patients and animal models was verified via cluster analysis. This model may be useful for the study of CVST pathophysiology and potential therapies.

Enhanced Medial Prefrontal Cortex and Hippocampal Activity Improves Memory Generalization in APP/PS1 Mice: A Multimodal Animal MRI Study.

Memory generalization allows individuals to extend previously learned movement patterns to similar environments, contributing to cognitive flexibility. In Alzheimer's disease (AD), the disturbance of generalization is responsible for the deficits of episodic memory, causing patients with AD to forget or misplace things, even lose track of the way home. Cognitive training can effectively improve the cognition of patients with AD through changing thinking mode and memory flexibility. In this study, a T-shaped maze was utilized to simulate cognitive training in APP/PS1 mice to elucidate the potential mechanisms of beneficial effects after cognitive training. We found that cognitive training conducted by a T-shaped maze for 4 weeks can improve the memory generalization ability of APP/PS1 mice. The results of functional magnetic resonance imaging (fMRI) showed that the functional activity of the medial prefrontal cortex (mPFC) and hippocampus was enhanced after cognitive training, and the results of magnetic resonance spectroscopy (MRS) showed that the neurochemical metabolism of N-acetyl aspartate (NAA) and glutamic acid (Glu) in mPFC, hippocampus and reuniens (Re) thalamic nucleus were escalated. Furthermore, the functional activity of mPFC and hippocampus was negatively correlated with the escape latency in memory generalization test. Therefore, these results suggested that cognitive training might improve memory generalization through enhancing the functional activity of mPFC and hippocampus and increasing the metabolism of NAA and Glu in the brain regions of mPFC, hippocampus and Re nucleus.

Differentiation of paediatric posterior fossa tumours by the multiregional and multiparametric MRI radiomics approach: a study on the selection of optimal multiple sequences and multiregions.

OBJECTIVE: To evaluate the diagnostic performance of a radiomics model based on multiregional and multiparametric MRI to classify paediatric posterior fossa tumours (PPFTs), explore the contribution of different MR sequences and tumour subregions in tumour classification, and examine whether contrast-enhanced T1 weighted (T1C) images have irreplaceable added value. METHODS: This retrospective study of 136 PPFTs extracted 11,958 multiregional (enhanced, non-enhanced, and total tumour) features from multiparametric MRI (T1- and T2 weighted, T1C, fluid-attenuated inversion recovery, and diffusion-weighted images). These features were subjected to fast correlation-based feature selection and classified by a support vector machine based on different tasks. Diagnostic performances of multiregional and multiparametric MRI features, different sequences, and different tumoral regions were evaluated using multiclass and one-vs-rest strategies. RESULTS: The established model achieved an overall area under the curve (AUC) of 0.977 in the validation cohort. The performance of PPFTs significantly improved after replacing T1C with apparent diffusion coefficient maps added into the plain scan sequences (AUC from 0.812 to 0.917). When oedema features were added to contrast-enhancing tumour volume, the performance did not significantly improve. CONCLUSION: The radiomics model built by multiregional and multiparametric MRI features allows for the excellent distinction of different PPFTs and provides valuable references for the rational adoption of MR sequences. ADVANCES IN KNOWLEDGE: This study emphasized that T1C has limited added value in predicting PPFTs and should be cautiously adopted. Selecting optimal MR sequences may help guide clinicians to better allocate acquisition sequences and reduce medical costs.

Activation of Adenosine Monophosphate-Activated Protein Kinase Drives the Aerobic Glycolysis in Hippocampus for Delaying Cognitive Decline Following Electroacupuncture Treatment in APP/PS1 Mice.

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.