Altered thalamus functional connectivity in patients with acute unilateral vestibulopathy: a resting-state fMRI study.

Objective: Acute unilateral vestibulopathy (AUVP) is the second leading cause of peripheral vestibular vertigo. Full recovery of AUVP is related to sufficient central vestibular compensation. It has been confirmed that the vestibular nucleus and vestibular cortex are involved in the process of vestibular compensatory in AUVP patients. However, few studies have focused on the functional compensation of thalamus in patients with AUVP. This study aimed to explore the alterations of resting-state functional connectivity (FC) focused on thalamus using functional magnetic resonance imaging (fMRI) in AUVP patients. Methods: Data of 3D-T1 and resting-state fMRI were collected from 40 AUVP patients and 35 healthy controls (HC). Seeds-based (bilateral thalamus) FC was analyzed to investigate the changes in FC between the two groups. Furthermore, we evaluated the associations between altered thalamus FC and clinical features in AUVP patients using Pearson's partial correlation. Results: Compared with HC, AUVP patients showed decreased FC between bilateral thalamus and left insula. We also observed decreased FC between right thalamus and left supramarginal gyrus. Additionally, we found increased FC between left thalamus and right postcentral gyrus (PCG), as well as increased FC between right thalamus and regions of bilateral PCG, right middle frontal gyrus and right middle occipital gyrus in AUVP patients. Furthermore, the FC between left thalamus and left insula was negatively correlated with values of canal paresis in patients with AUVP (p = 0.010, r = -0.434). Conclusion: Our results provided first evidence for the decreased thalamo-vestibular cortex pathway, as well as increased thalamo-somatosensory and thalamo-visual cortex pathway in AUVP patients. These findings help us better understand the underlying mechanisms of central dynamic compensatory following an acute unilateral peripheral vestibular damage.

A one-year relapse prediction model for acute ischemic stroke (AIS) based on clinical big data.

Objective: To develop and evaluate a nomogram prediction model for recurrence of acute ischemic stroke (AIS) within one year. Method: Patients with AIS treated at the second affiliated hospital of Xuzhou Medical University from August 2017 to July 2019 were enrolled. Clinical data such as demographic data, risk factors, laboratory tests, TOAST etiological types, MRI features, and treatment methods were collected. Cox regression analysis was done to determine the parameters for entering the nomogram model. The performance of the model was estimated by receiver operating characteristic curves, decision curve analysis, calibration curves, and C-index. Result: A total of 645 patients were enrolled in this study. Side of hemisphere (SOH, Bilateral, HR = 0.35, 95 % CI = 0.15-0.84, p = 0.018), homocysteine (HCY, HR = 1.38, 95 % CI = 1.29-1.47, p < 0.001), c-reactive protein (CRP, HR = 1.04, 95 % CI = 1.01-1.07, p = 0.013) and stroke severity (SS, HR = 3.66, 95 % CI = 2.04-6.57, p < 0.001) were independent risk factors. The C-index of the nomogram model was 0.872 (se = 0.016). The area under the receiver operating characteristic (ROC)curve at one-year recurrence was 0.900. Calibration curve, decision curve analysis showed good performance of the nomogram. The cutoff value for low or high risk of recurrence score was 1.73. Conclusion: The nomogram model for stroke recurrence within one year developed in this study performed well. This useful tool can be used in clinical practice to provide important guidance to healthcare professionals.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study.

BACKGROUND: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods. METHODS: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored. RESULTS: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05). CONCLUSIONS: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Fractional Amplitude of Low-Frequency Fluctuation and Voxel-Mirrored Homotopic Connectivity in Patients with Persistent Postural-Perceptual Dizziness: Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: Persistent postural-perception dizziness (PPPD) is a chronic subjective form of dizziness characterized by the exacerbation of dizziness with active or passive movement, complex visual stimuli, and upright posture. Therefore, we aimed to analyze the resting-state functional magnetic resonance imaging (fMRI) in patients with PPPD using fractional amplitude of low-frequency fluctuation (fALFF) and voxel-mirrored homotopic connectivity (VMHC) and evaluate the correlation between abnormal regions in the brain and clinical features to investigate the pathogenesis of PPPD. Methods: Thirty patients with PPPD (19 females and 11 males) and 30 healthy controls (HCs; 18 females and 12 males) were closely matched for age and sex. The fALFF and VMHC methods were used to investigate differences in fMRI (BOLD sequences) between the PPPD and HC groups and to explore the associations between areas of functional abnormality and clinical characteristics (dizziness, anxiety, depression, and duration). Result: Compared to the HC group, patients with PPPD displayed different functional change patterns, with increased fALFF in the right precuneus and decreased VMHC in the bilateral precuneus. In addition, patients with PPPD had a positive correlation between precuneus fALFF values and dizziness handicap inventory (DHI) scores, and a negative correlation between VMHC values and the disease duration. Conclusions: Precuneus dysfunction was observed in patients with PPPD. The fALFF values correlated with the degree of dizziness in PPPD, and changes in VMHC values were associated with the duration of dizziness, suggesting that fMRI changes in the precuneus of patients could be used as a potential imaging marker for PPPD.

Increased functional connectivity between default mode network and visual network potentially correlates with duration of residual dizziness in patients with benign paroxysmal positional vertigo.

Objective: To assess changes in static and dynamic functional network connectivity (sFNC and dFNC) and explore their correlations with clinical features in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning maneuvers (CRM) using resting-state fMRI. Methods: We studied resting-state fMRI data from 39 BPPV patients with RD compared to 38 BPPV patients without RD after successful CRM. Independent component analysis and methods of sliding window and k-means clustering were adopted to investigate the changes in dFNC and sFNC between the two groups. Additionally, temporal features and meta-states were compared between the two groups. Furthermore, the associations between fMRI results and clinical characteristics were analyzed using Pearson's partial correlation analysis. Results: Compared with BPPV patients without RD, patients with RD had longer duration of BPPV and higher scores of dizziness handicap inventory (DHI) before successful CRM. BPPV patients with RD displayed no obvious abnormal sFNC compared to patients without RD. In the dFNC analysis, patients with RD showed increased FNC between default mode network (DMN) and visual network (VN) in state 4, the FNC between DMN and VN was positively correlated with the duration of RD. Furthermore, we found increased mean dwell time (MDT) and fractional windows (FW) in state 1 but decreased MDT and FW in state 3 in BPPV patients with RD. The FW of state 1 was positively correlated with DHI score before CRM, the MDT and FW of state 3 were negatively correlated with the duration of BPPV before CRM in patients with RD. Additionally, compared with patients without RD, patients with RD showed decreased number of states and state span. Conclusion: The occurrence of RD might be associated with increased FNC between DMN and VN, and the increased FNC between DMN and VN might potentially correlate with the duration of RD symptoms. In addition, we found BPPV patients with RD showed altered global meta-states and temporal features. These findings are helpful for us to better understand the underlying neural mechanisms of RD and potentially contribute to intervention development for BPPV patients with RD.

MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation.

BACKGROUND: Neuroinflammation contributes to both epileptogenesis and the associated neurodegeneration, so regulation of inflammatory signaling is a potential strategy for suppressing epilepsy development and pathological progression. Exosomes are enriched in microRNAs (miRNAs), considered as vital communication tools between cells, which have been proven as potential therapeutic method for neurological disease. Here, we investigated the role of miR129-5p-loaded mesenchymal stem cell (MSC)-derived exosomes in status epilepticus (SE) mice model. METHODS: Mice were divided into four groups: untreated control (CON group), kainic acid (KA)-induced SE groups (KA group), control exosome injection (KA + Exo-con group), miR129-5p-loaded exosome injection (KA + Exo-miR129-5p group). Hippocampal expression levels of miR129-5p, HMGB1, and TLR4 were compared among groups. Nissl and Fluoro-jade B staining were conducted to evaluate neuronal damage. In addition, immunofluorescence staining for IBA-1 and GFAP was performed to assess glial cell activation, and inflammatory factor content was determined by ELISA. Hippocampal neurogenesis was assessed by BrdU staining. RESULTS: The expression of HMGB1 was increased after KA-induced SE and peaking at 48 h, while hippocampal miR129-5p expression decreased in SE mice. Exo-miR129-5p injection reversed KA-induced upregulation of hippocampal HMGB1 and TLR4, alleviated neuronal damage in the hippocampal CA3, reduced IBA-1 + and GFAP + staining intensity, suppressed SE-associated increases in inflammatory factors, and decreased BrdU + cell number in dentate gyrus. CONCLUSIONS: Exosomes loaded with miR129-5p can protect neurons against SE-mediated degeneration by inhibiting the pro-inflammatory HMGB1/TLR4 signaling axis.

Altered parietal operculum cortex 2 functional connectivity in benign paroxysmal positional vertigo patients with residual dizziness: A resting-state fMRI study.

AIMS: To investigate changes in functional connectivity (FC) focusing on parietal operculum cortex 2 (OP2) in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning procedure (CRP). METHODS: High-resolution three-dimensional T1 and resting-state functional magnetic resonance imaging (fMRI) were performed on 55 healthy controls (HCs), 55 BPPV patients with RD, and 55 patients without RD after successful CRP. Seed-based (bilateral OP2) FC was calculated to investigate the changes in FC among the three groups. Additionally, we further explored the associations between abnormal FC and clinical symptoms. RESULTS: One-way analysis of covariance showed significant FC differences among the three groups. Post-hoc analysis showed that patients with RD exhibited decreased FC between left OP2 and regions of left angular gyrus (AG), thalamus, precuneus, middle frontal gyrus (MFG), and right cerebellum posterior lobe (CPL) in comparison with HCs. In addition, compared with patients without RD, patients with RD showed decreased FC between left OP2 and regions of left MFG, AG, middle temporal gyrus, and right CPL. Moreover, in patients with RD, the FC between left thalamus and OP2 was negatively correlated with duration of RD, and the FC between left AG and OP2 was negatively correlated with duration of BPPV. CONCLUSION: BPPV patients with RD showed reduced FC between brain regions involved in vestibular processing and spatial cognition; These results suggested that BPPV patients with RD might have diminished central processing of vestibular information and impaired spatial cognition.

Association between the Composite Dietary Antioxidant Index and Stroke: A cross-sectional Study.

The composite dietary antioxidant index (CDAI) is indeed a valuable nutritional tool used to evaluate the overall antioxidant capacity of an individual's daily food consumption. The CDAI was calculated from the intake of six antioxidant components in the diet, including vitamin A, vitamin C and vitamin E, carotenoids, selenium, and zinc. This study aimed to determine the association between CDAI and stroke. Utilizing data from the 2003-2018 NHANES dataset, CDAI was computed by summarizing the intake of six dietary antioxidants based on 24-hour dietary recall interviews. The relationship between CDAI and stroke was examined using multivariate logistic regression and restricted cubic spline analysis. This study ultimately included 39,432 participants, of whom 1,527 (3.87%) had a stroke. The multivariate logistic regression model 3 that fully adjusted all confounding variables showed a negative association between CDAI and stroke (OR = 0.97; 95% CI:0.95, 0.99). The highest tertile of CDAI saw a 23% drop in the prevalence of stroke compared to the lowest tertile (OR = 0.77; 95%CI: 0.64,0.92). Restricted cubic spline suggested that this negative correlation was nonlinear with an inflection point of -2.99. Subgroup analyses and interaction tests showed that this negative correlation was more applicable in patients with prediabetes (P < 0.05). There was a non-linear negative correlation between CDAI level and stroke prevalence, and this correlation was more significant in people with pre-diabetes. Appropriate CDAI levels may contribute to the management of stroke risk.

A clinical prediction model based on interpretable machine learning algorithms for prolonged hospital stay in acute ischemic stroke patients: a real-world study.

Objective: Acute ischemic stroke (AIS) brings an increasingly heavier economic burden nowadays. Prolonged length of stay (LOS) is a vital factor in healthcare expenditures. The aim of this study was to predict prolonged LOS in AIS patients based on an interpretable machine learning algorithm. Methods: We enrolled AIS patients in our hospital from August 2017 to July 2019, and divided them into the "prolonged LOS" group and the "no prolonged LOS" group. Prolonged LOS was defined as hospitalization for more than 7 days. The least absolute shrinkage and selection operator (LASSO) regression was applied to reduce the dimensionality of the data. We compared the predictive capacity of extended LOS in eight different machine learning algorithms. SHapley Additive exPlanations (SHAP) values were used to interpret the outcome, and the most optimal model was assessed by discrimination, calibration, and clinical utility. Results: Prolonged LOS developed in 149 (22.0%) of the 677 eligible patients. In eight machine learning algorithms, prolonged LOS was best predicted by the Gaussian naive Bayes (GNB) model, which had a striking area under the curve (AUC) of 0.878 ± 0.007 in the training set and 0.857 ± 0.039 in the validation set. The variables sorted by the gap values showed that the strongest predictors were pneumonia, dysphagia, thrombectomy, and stroke severity. High net benefits were observed at 0%-76% threshold probabilities, while good agreement was found between the observed and predicted probabilities. Conclusions: The model using the GNB algorithm proved excellent for predicting prolonged LOS in AIS patients. This simple model of prolonged hospitalization could help adjust policies and better utilize resources.

Altered functional activity of the precuneus and superior temporal gyrus in patients with residual dizziness caused by benign paroxysmal positional vertigo.

Objective: Benign paroxysmal positional vertigo (BPPV) is a common clinical vertigo disease, and the most effective treatment for this disease is canal repositioning procedures (CRP). Most patients return to normal after a single treatment. However, some patients still experience residual dizziness (RD) after treatment, and this disease's pathogenesis is currently unclear. The purpose of this study is to explore whether there are abnormal brain functional activities in patients with RD by using resting-state functional magnetic resonance imaging (rs-fMRI) and to provide imaging evidence for the study of the pathogenesis of RD. Materials and methods: The BPPV patients in the Second Affiliated Hospital of Xuzhou Medical University had been included from December 2021 to November 2022. All patients had been received the collection of demographic and clinical characteristics (age, gender, involved semicircular canal, affected side, CRP times, BPPV course, duration of RD symptoms, and whether they had hypertension, diabetes, coronary heart disease.), scale assessment, including Dizziness Handicap Inventory (DHI), Hamilton Anxiety Inventory (HAMA), Hamilton Depression Inventory (HAMD), rs-fMRI data collection, CRP treatment, and then a one-month follow-up. According to the follow-up results, 18 patients with RD were included. At the same time, we selected 19 healthy individuals from our hospital's physical examination center who matched their age, gender as health controls (HC). First, the amplitude of low-frequency fluctuations (ALFF) analysis method was used to compare the local functional activities of the two groups of subjects. Then, the brain regions with different ALFF results were extracted as seed points. Functional connectivity (FC) analysis method based on seed points was used to explore the whole brain FC of patients with RD. Finally, a correlation analysis between clinical features and rs-fMRI data was performed. Results: Compared to the HC, patients with RD showed lower ALFF value in the right precuneus and higher ALFF value in the right superior temporal gyrus (STG). When using the right STG as a seed point, it was found that the FC between the right STG, the right supramarginal gyrus (SMG), and the left precuneus was decreased in RD patients. However, no significant abnormalities in the FC were observed when using the right precuneus as a seed point. Conclusion: In patients with RD, the local functional activity of the right precuneus is weakened, and the local functional activity of the right STG is enhanced. Furthermore, the FC between the right STG, the right SMG, and the left precuneus is weakened. These changes may explain the symptoms of dizziness, floating sensation, walking instability, neck tightness, and other symptoms in patients with RD to a certain extent.