This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

Background Internal capsule strokes often result in multidomain cognitive impairments across memory, attention, and executive function, typically due to disruptions in brain network connectivity. Our study examines these impairments by analyzing interactions within the triple-network model, focusing on both static and dynamic aspects. Methods We collected resting-state fMRI data from 62 left (CI_L) and 56 right (CI_R) internal capsule stroke patients, along with 57 healthy controls (HC). Using independent component analysis to extract the default mode (DMN), executive control (ECN), and salience networks (SAN), we conducted static and dynamic functional network connectivity analyses (DFNC) to identify differences between stroke patients and controls. For DFNC, we used k-means clustering to focus on temporal properties and multilayer network analysis to examine integration and modularity Q, where integration represents dynamic interactions between networks, and modularity Q measures how well the network is divided into distinct modules. We then calculated the correlations between SFNC/DFNC properties with significant inter-group differences and cognitive scales. Results Compared to HC, both CI_L and CI_R patients showed increased static FCs between SAN and DMN and decreased dynamic interactions between ECN and other networks. CI_R patients also had heightened static FCs between SAN and ECN and maintained a state with strongly positive FNCs across all networks in the triple-network model. Additionally, CI_R patients displayed decreased modularity Q. Conclusion These findings highlight that stroke can result in the disruption of static and dynamic interactions in the triple network model, aiding our understanding of the neuropathological basis for multidomain cognitive deficits after internal capsule stroke.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconveniencethis may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

The risk for motor and cognitive impairment is increased in patients with chronic pontine infarction (PI). In this study, we attempted to explore the alterations of neurovascular coupling (NVC) in order to understand the neural basis of behavioral impairment after PI. Three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied in 49 patients with unilateral PI (left-sided, n = 26; right-sided, n = 23) and 30 matched normal subjects to assess whole-brain cerebral blood flow (CBF) and functional connectivity strength (FCS). We evaluated NVC in each subject by calculating the correlation coefficient between the whole-brain CBF and FCS (CBF-FCS coupling) and the ratio between voxel-wise CBF and FCS (CBF/FCS ratio). The FCS maps were then divided into long-range and short-range FCS to identify the influence of connection distance. The results indicated that the CBF-FCS coupling in the whole-brain level was significantly interrupted in PI patients, and the CBF/FCS ratio in cognition-related brain regions was abnormal. Distance-dependent results demonstrated that PI had a more serious effect on long-range neuro-vascular coupling. Correlation analysis revealed that the changes in neurovascular coupling were correlated with working memory scores. These findings imply that disruption of neurovascular coupling in the remote-infarction brain regions may underlie the impaired cognitive functions in chronic PI.

To explore the mechanisms of cognitive impairment and reorganization in patients with left- and right-sided capsular stroke (CS_L, CS_R), we collected resting-state fMRI data from 62 CS_L, 56 CS_R patients and 57 normal controls (NC). Based on the triple-network model [involving the default mode, central executive and salience networks], static (SFNC) and dynamic functional network connectivities (DFNC) were performed to calculate inter-network functional connectivities and estimate temporal features in each state among the three groups. We found more significant SFNC and DFNC changes in CS_R group, suggesting more extensive cognitive impairment and reorganization in CS_R patients than those with CS_L.

Cognitive dysfunction in patients with infratentorial stroke has been paid little attention. Brainstem stroke may disrupt network connectivity across the whole brain and affect multidomain cognition, but the details of this process remain unclear. The study aimed to investigate the effects of stroke-induced pontine injury on whole-brain network connectivity and cognitive function. We included 47 patients with pontine stroke and 56 healthy comparisons (HC), who underwent cognitive tests and functional magnetic resonance imaging (fMRI). Seven meaningful brain networks were identified using independent component analysis (ICA). Patients with pontine stroke had decreased intra-network functional connectivities (FCs) in the primary perceptual and higher cognitive control networks, including sensorimotor network (SMN), visual network (VIS), default mode network (DMN), and salience network (SAN), as well as decreased inter-network FCs in the primary perceptual (VIS-SMN) and higher cognitive control networks (bilateral frontoparietal networks, rFPN-lFPN). While the FCs between the primary perceptual and higher cognitive control networks (VIS-DMN, VIS-rFPN, VIS-lFPN) were increased. Furthermore, the alterations in these FCs correlated with patients' cognitive measurements. These findings suggested that the infratentorial stroke can induce dysfunctional connectivity in both primary perceptual and higher cognitive control networks at the whole-brain level, which may be attributable to the neural substrates of multidomain cognitive deficits in these patients.

Objectives To investigate the longitudinal changes in gray matter volume (GMV) and functional connectivity (FC) in patients with pontine infarction (PI) during a 6-month follow-up period. Methods Twenty-two patients underwent MRI scans and behavioral assessments at 1 week, 1 month, 3 months, and 6 months after PI. Twenty-two normal controls (NC) were administered once with a similar examination. Voxel-wise GMV analysis was used to investigate the difference between the 1 week of PI and NC groups. Longitudinal changes in GMV were assessed and then used as seed regions to explore the accompanying FC changes during the 6-month follow-up. Correlations of the behavioral scores with the imaging indices of clusters with altered GMV and FC were also investigated. Results The LPI group exhibited GMV atrophy in the left cerebellar Crus II, right cerebellar lobule VI, right Vermis VI, while the RPI group showed GMV atrophy in the left cerebellar Crus II. The significant decrease of GMV firstly appeared at 1 month and gradually decreased over time. When using brain regions with GMV atrophy as seeds, longitudinal analysis of FC showed a significant decrease between the left cerebellar Crus II and left middle frontal gyrus at 6 months in the LPI group. Furthermore, the longitudinally altered FC values were negatively correlated with motor scores over time. Conclusion These findings provide evidence for progressive GMV atrophy in the cerebellum and impaired relative FC in patients with PI, which could provide vital information for investigating neural bases of behavioral recovery in PI.

Neurological deficits after stroke are closely related to white matter microstructure damage. However, secondary changes in white matter microstructure after pontine infarction (PI) in the whole brain remain unclear. This study aimed to investigate the correlation of diffusion kurtosis imaging (DKI)-derived diffusion and kurtosis parameters of abnormal white matter tracts with behavioral function in patients with chronic PI. Overall, 60 patients with unilateral chronic PI (33 patients with left PI and 27 patients with right PI) and 30 normal subjects were recruited and underwent DKI scans. Diffusion parameters derived from diffusion tensor imaging (DTI) and DKI and kurtosis parameters derived from DKI were obtained. Between-group differences in multiple parameters were analyzed to assess the changes in abnormal white matter microstructure. Moreover, we also calculated the sensitivities of different diffusion and kurtosis parameters of DTI and DKI for identifying abnormal white matter tracts. Correlations between the DKI-derived parameters in secondary microstructure changes and behavioral scores in the PI were analyzed. Compared with the NC group, both left PI and right PI groups showed more extensive perilesional and remote white matter microstructure changes. The DKI-derived diffusion parameters showed higher sensitivities than did the DTI-derived parameters. Further, DKI-derived diffusion and kurtosis parameters in abnormal white matter regions were correlated with impaired motor and cognitive function in patients with PI. In conclusion, PI could lead to extensive white matter tracts impairment in perilesional and remote regions. Further, the diffusion and kurtosis parameters could be complementary for identifying comprehensive tissue microstructural damage after PI.

Recent neuroimaging studies have shown the possibility of cognitive impairment after pontine stroke. In this study, we aimed to use voxel-mirrored homotopic connectivity (VMHC) to investigate changes in the cognitive function in chronic pontine stroke. Functional MRI (fMRI) and behavioral assessments of cognitive function were obtained from 56 patients with chronic pontine ischemic stroke [28 patients with left-sided pontine stroke (LP) and 28 patients with right-sided pontine stroke (RP)] and 35 matched healthy controls (HC). The one-way ANOVA test was performed for the three groups after the VMHC analysis. Results showed that there were significant decreases in the bilateral lingual gyrus (Lingual_L and Lingual_R) and the left precuneus (Precuneus_L) in patients with chronic pontine ischemic stroke compared to HCs. However, in a post-hoc multiple comparison test, this difference remained only between the HC and RP groups. Moreover, we explored the relationship between the decreased z -values in VMHC and the behavior-task scores using a Pearson's correlation test and found that both scores of short-term memory and long-term memory in the Rey Auditory Verbal Learning Test were positively correlated with z -values of the left lingual gyrus (Lingual_L), the right lingual gyrus (Lingual_R), and the left precuneus (Precuneus_L) in VMHC. Besides that, the z -values of Precuneus_L in VMHC were also negatively correlated with the reaction time for correct responses in the Flanker task and the spatial memory task. In conclusion, first, the lingual gyrus played an important role in verbal memory. Second, the precuneus influenced the working memory, both auditory-verbal memory and visual memory. Third, the right-sided stroke played a greater role in the results of this study. This study provides a basis for further elucidation of the characteristics and mechanisms of cognitive impairment after pontine stroke.

目的 采用3D动脉自旋标记(arterial spin labeling,ASL)灌注成像评估运动功能恢复较好的慢性期皮层下脑梗死患者的静息态脑血流量(cerebral blood flow,CBF),并分析其与认知功能中执行能力的关系.材料与方法 采用GE Discovery MR 750扫描仪对29例慢性期脑梗死患者及30例健康志愿者行3D动脉自旋标记灌注成像.以SPM8中的GLM(一般线性模型)为参考,把教育年限、年龄、性别当作协变量,把"全脑灰质模板"当作mask,实施独立样本t检验,明确对照组、病例组脑血流量不同的脑区,并对其同执行能力间的联系展开讨论.结果 相较于对照组,患者健侧缘上回(supramarginal gyrus,SMG)与额上回(superior frontal gyrus,SFG)脑血流量皆显著增加(P<0.05).上述2个脑区的CBF值皆于连线测试B的反应时间呈负向相关.结论 运动功能有效恢复的慢性期皮层下脑梗死患者远隔病灶的皮层区CBF仍存在异常,同时此部位CBF的改变同认知功能中的执行能力存在相关性.

Our aim was to identify the longitudinal changes in gray matter volume (GMV) and secondary alterations of structural covariance after pontine stroke (PS). Structural MRI and behavioral scores were obtained at 1 week, 1 month, 3 months, 6 months in 11 patients with PS. Twenty healthy subjects underwent the same examination only once. We used voxel-based morphometry and seed-based structural covariance to investigate the altered GMV and structural covariance patterns. Furthermore, the associations between the GMV changes and behavioral scores were assessed. With the progression of the disease, GMV decreased significantly in the bilateral cerebellar posterior lobe (ipsilateral Crus II (CBE Crus II_IL) and contralateral Crus I (CBE Crus I_CL)), which were initially detected at the first month and then continued to decrease during the following 6 months. Based on the CBE Crus II_IL and CBE Crus I_CL as seed regions, structural covariance analysis revealed that there were more positively and negatively correlated brain regions in PS group, mainly distributed in the bilateral prefrontal lobe, parietal lobe, temporal lobe, paralimbic system and cerebellum. In addition, PS group showed more additional correlations between these covariant brain regions, and the changes of GMV in these regions were correlated with behavioral scores related to motor and cognitive functions. These findings indicate that PS could lead to significant GMV atrophy in the bilateral cerebellar posterior lobe at the early stage, accompanied by anomalous structural covariance patterns with more covariant brain regions and additional structural connectivity, which may provide useful information for understanding the neurobiological mechanisms of behavioral recovery after PS.

Abnormal cerebral blood flow (CBF) and resting-state functional connectivity (rs-FC) are sensitive biomarkers of disease progression and prognosis. This study investigated neural underpinnings of motor and cognitive recovery by longitudinally studying the changes of CBF and FC in pontine infarction (PI). Twenty patients underwent three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL), resting-state functional magnetic resonance imaging (rs-fMRI) scans, and behavioral assessments at 1 week, 1, 3, and 6 months after stroke. Twenty normal control (NC) subjects underwent the same examination once. First, we investigated CBF changes in the acute stage, and longitudinal changes from 1 week to 6 months after PI. Brain regions with longitudinal CBF changes were then used as seeds to investigate longitudinal FC alterations during the follow-up period. Compared with NC, patients in the left PI (LPI) and right PI (RPI) groups showed significant CBF alterations in the bilateral cerebellum and some supratentorial brain regions at the baseline stage. Longitudinal analysis revealed that altered CBF values in the right supramarginal (SMG_R) for the LPI group, while the RPI group showed significantly dynamic changes of CBF in the left calcarine sulcus (CAL_L), middle occipital gyrus (MOG_L), and right supplementary motor area (SMA_R). Using the SMG_R as the seed in the LPI group, FC changes were found in the MOG_L, middle temporal gyrus (MTG_L), and prefrontal lobe (IFG_L). Correlation analysis showed that longitudinal CBF changes in the SMG_R and FC values between the SMG_R and MOG_L were associated with motor and memory scores in the LPI group, and longitudinal CBF changes in the CAL_L and SMA_R were related to memory and motor recovery in the RPI group. These longitudinal CBF and accompany FC alterations may provide insights into the neural mechanism underlying functional recovery after PI, including that of motor and cognitive functions.

Background: Previous studies on brain functional connectivity have revealed the neural physiopathology in patients with pontine stroke (PS). However, those studies focused only on the static features of intrinsic fluctuations, rather than on the time-varying effects throughout the entire scan. In the present study, we sought to explore the underlying mechanism of PS using the dynamic functional network connectivity (dFNC) method. Methods: Resting-state functional magnetic resonance imaging (fMRI) data were collected from 58 patients with PS and 52 healthy controls (HC). Independent component analysis (ICA), the sliding window method, and k-means clustering analysis were performed to extract different functional networks, to calculate dFNC matrices, and to estimate distinct dynamic connectivity states. Additionally, temporal features were compared between the two groups in each state to explore the brain’s preference for different dynamic connectivity states in PS, and global and local efficiency were compared among states to explore the differences of topologic organization across different dFNC states. The correlations between clinical scales and the temporal features that differed between the two groups also were calculated. Results: The dFNC analyses suggested four recurring states; in two of these states, the PS group showed a different duration from that of the HC group. Patients with PS spent significantly more time in a sparsely connected state (State 1), which was characterized by relatively low levels of connectivity within and between all brain networks. In contrast, patients with PS spent significantly less time in a highly segregated state (State 2), which was characterized by high levels of positive connectivities within primary perceptional domains and within higher cognitive control domains, and by high levels of negative inter-functional connectivities (inter-FCs) among primary perceptional and higher cognitive control domains. Additionally, the dwell time in State 2 was positively correlated with HC group’s long-term memory scores in the Rey Auditory Verbal Learning Test (RAVLT-L), whereas there was no correlation between the State-2 dwell time and RAVLT-L scores in the PS group. Furthermore, the sparsely connected state and the highly segregated state mentioned above had the highest global efficiency and the highest local efficiency among the four states, respectively. Conclusions: In summary, we observed a preference in the aberrant brain for dynamic connectivity states with different network topologic organization in patients with PS, indicating abnormal functional segregation and integration of the whole brain and confirming the imperfection of functional network connectivity in patients with PS. These findings provide new evidence for the dynamic neural mechanisms underlying clinical symptoms in patients with PS.