scholarly journals Acute ischemic stroke alters the brain’s preference for distinct dynamic connectivity states

2019 ◽  
Author(s):  
Anna K. Bonkhoff ◽  
Flor A. Espinoza ◽  
Harshvardhan Gazula ◽  
Victor M. Vergara ◽  
Lukas Hensel ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Resting State ◽  
Network Connectivity ◽  
Resting State Fmri ◽  
Cortical Reorganization ◽  
Connectivity Pattern ◽  
Healthy Controls ◽  
Stroke Patients ◽  
Dynamic Connectivity

AbstractAcute ischemic stroke disturbs healthy brain organization, prompting subsequent plasticity and reorganization to compensate for loss of specialized neural tissue and function. Static resting-state functional magnetic resonance imaging (fMRI) studies have already furthered our understanding of cerebral reorganization by estimating stroke-induced changes in network connectivity aggregated over the duration of several minutes. In this study, we utilized dynamic resting-state fMRI analyses to increase temporal resolution to seconds and explore transient configurations of motor network connectivity in acute stroke. To this end, we collected resting-state fMRI data of 31 acute ischemic stroke patients and 17 age-matched healthy controls. Stroke patients presented with moderate to severe hand motor deficits. By estimating dynamic connectivity within a sliding window framework, we identified three distinct connectivity configurations of motor-related networks. Motor networks were organized into three regional domains, i.e. a cortical, subcortical and cerebellar domain. Temporal connectivity patterns of stroke patients markedly diverged from those of healthy controls depending on the severity of the initial motor impairment. Moderately affected patients (n=18) spent significantly more time in a weakly connected configuration that was characterized by low levels of connectivity, both locally as well as between distant regions. In contrast, severely affected patients (n=13) showed a significant preference for transitions into a spatially segregated connectivity configuration. This configuration featured particularly high levels of local connectivity within the three regional domains as well as anti-correlated connectivity between distant networks across domains. A third connectivity configuration represented an intermediate connectivity pattern compared to the preceding two, and predominantly encompassed decreased inter-hemispheric connectivity between cortical motor networks independent of individual deficit severity. Alterations within this third configuration thus closely resembled previously reported ones originating from static resting-state fMRI studies post-stroke.In summary, acute ischemic stroke not only prompted changes in connectivity between distinct functional networks, yet also caused severe aberrations in temporal properties of large-scale network interactions depending on the individual deficit severity. These findings offer new vistas on the dynamic neural mechanisms underlying acute neurological symptoms, cortical reorganization and treatment effects in stroke patients.

scholarly journals Acute ischaemic stroke alters the brain’s preference for distinct dynamic connectivity states

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1525-1540 ◽  
Author(s):  
Anna K Bonkhoff ◽  
Flor A Espinoza ◽  
Harshvardhan Gazula ◽  
Victor M Vergara ◽  
Lukas Hensel ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Functional Mri ◽  
Acute Ischaemic Stroke ◽  
Resting State ◽  
Network Connectivity ◽  
Cortical Reorganization ◽  
Connectivity Pattern ◽  
Stroke Patients ◽  
Mri Studies ◽  
Dynamic Connectivity

Abstract Acute ischaemic stroke disturbs healthy brain organization, prompting subsequent plasticity and reorganization to compensate for the loss of specialized neural tissue and function. Static resting state functional MRI studies have already furthered our understanding of cerebral reorganization by estimating stroke-induced changes in network connectivity aggregated over the duration of several minutes. In this study, we used dynamic resting state functional MRI analyses to increase temporal resolution to seconds and explore transient configurations of motor network connectivity in acute stroke. To this end, we collected resting state functional MRI data of 31 patients with acute ischaemic stroke and 17 age-matched healthy control subjects. Stroke patients presented with moderate to severe hand motor deficits. By estimating dynamic functional connectivity within a sliding window framework, we identified three distinct connectivity configurations of motor-related networks. Motor networks were organized into three regional domains, i.e. a cortical, subcortical and cerebellar domain. The dynamic connectivity patterns of stroke patients diverged from those of healthy controls depending on the severity of the initial motor impairment. Moderately affected patients (n = 18) spent significantly more time in a weakly connected configuration that was characterized by low levels of connectivity, both locally as well as between distant regions. In contrast, severely affected patients (n = 13) showed a significant preference for transitions into a spatially segregated connectivity configuration. This configuration featured particularly high levels of local connectivity within the three regional domains as well as anti-correlated connectivity between distant networks across domains. A third connectivity configuration represented an intermediate connectivity pattern compared to the preceding two, and predominantly encompassed decreased interhemispheric connectivity between cortical motor networks independent of individual deficit severity. Alterations within this third configuration thus closely resembled previously reported ones originating from static resting state functional MRI studies post-stroke. In summary, acute ischaemic stroke not only prompted changes in connectivity between distinct networks, but it also caused characteristic changes in temporal properties of large-scale network interactions depending on the severity of the individual deficit. These findings offer new vistas on the dynamic neural mechanisms underlying acute neurological symptoms, cortical reorganization and treatment effects in stroke patients.

scholarly journals Dynamic functional connectivity analysis reveals transiently increased segregation in patients with severe stroke

2020 ◽  
Author(s):  
Anna K. Bonkhoff ◽  
Markus D. Schirmer ◽  
Martin Bretzner ◽  
Mark Etherton ◽  
Kathleen Donahue ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Network Connectivity ◽  
Functional Network ◽  
Angular Gyrus ◽  
Stroke Severity ◽  
Functional Network Connectivity ◽  
Dynamic Connectivity ◽  
Dynamic Functional Network Connectivity

AbstractBackground and PurposeTo explore the whole-brain dynamic functional network connectivity patterns in acute ischemic stroke (AIS) patients and their relation to stroke severity in the short and long term.MethodsWe investigated large-scale dynamic functional network connectivity of 41 AIS patients two to five days after symptom onset. Re-occurring dynamic connectivity configurations were obtained using a sliding window approach and k-means clustering. We evaluated differences in dynamic patterns between three NIHSS-stroke severity defined groups (mildly, moderately, and severely affected patients). Furthermore, we established correlation analyses between dynamic connectivity estimates and AIS severity as well as neurological recovery within the first 90 days after stroke (DNIHSS). Finally, we built Bayesian hierarchical models to predict acute ischemic stroke severity and examine the inter-relation of dynamic connectivity and clinical measures, with an emphasis on white matter hyperintensity lesion load.ResultsWe identified three distinct dynamic connectivity configurations in the early post-acute stroke phase. More severely affected patients (NIHSS 10–21) spent significantly more time in a highly segregated dynamic connectivity configuration that was characterized by particularly strong connectivity (three-level ANOVA: p<0.05, post hoc t-tests: p<0.05, FDR-corrected for multiple comparisons). Recovery, as indexed by the realized change of the NIHSS over time, was significantly linked to the acute dynamic connectivity between bilateral intraparietal lobule and left angular gyrus (Pearson’s r = –0.68, p<0.05, FDR-corrected). Increasing dwell times, particularly those in a very segregated connectivity configuration, predicted higher acute stroke severity in our Bayesian modelling framework.ConclusionsOur findings demonstrate transiently increased segregation between multiple functional domains in case of severe AIS. Dynamic connectivity involving default mode network components significantly correlated with recovery in the first three months post-stroke.

Abstract W P29: Tissue Plasminogen Activator Mediated Reperfusion, and Subsequent Improvement in Resting State Connectivity Correlates with Functional Outcome in Acute Ischemic Stroke Patients

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Souvik Sen ◽  
Johann Fridriksson ◽  
Taylor Hanayik ◽  
Christopher Rorden ◽  
Isabel Hubbard ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Connectivity ◽  
Functional Outcome ◽  
Resting State ◽  
Network Connectivity ◽  
Stroke Patients ◽  
Post Stroke ◽  
Resting State Network ◽  
Tissue Plasminogen

Background: Intravenous Tissue Plasminogen Activator (TPA) is the only FDA approved medical therapy for acute ischemic stroke (AIS). Prior study suggests that early recanalization is associated with better stroke outcome. Our aim was to correlate task-negative and task-positive (TN/TP) resting state network activity with tissue perfusion and functional outcome, in stroke patients who received TPA. Method: AIS patients were consented and underwent NIH stroke scale (NIHSS) assessment and magnetic resonance imaging (MRI) scans during TPA infusion (baseline) and six hours post stroke. The MRI sequences include contrast-enhanced perfusion weighted image (PWI) and resting state Blood Oxygen Level-Dependent or BOLD (RSB) images acquired using a Siemens Treo 3T MRI scanner. Additionally, the RSB scan and the NIHSS were obtained at a 30-day follow up visit. Results: Fourteen patients (mean age ± SD=63 ±14, 50% male, 50% white, 43% black and 7% others) who qualified for TPA completed the study at baseline and 6 hours post stroke. Of these, 6 patients had valid follow up data at 30 days. Three patients without cerebral ischemia were excluded. A paired samples t-test comparing baseline and 6h post stroke showed a significantly improved TP network t(10)= -4.24 p< 0.05. The resting network connectivity improved from 6 hours post stroke to 30-days follow up, t(5)= -5.35 p< 0.01. Similarly, NIHSS, at 6h post stroke t(10)= 3.62 p< 0.01 and at 30-days follow up t(5)= -3.4 p< 0.01 were significantly better than the NIHSS at baseline. The 6-hours post-stroke perfusion correlated with the resting network connectivity in both the damaged (r=-0.56 p= 0.07) and intact hemispheres (r= -0.57 p= 0.06). Differences in functional connectivity and NIHSS scores from baseline to 6 h were positively correlated (r= 0.56 p=0.07). Conclusion: In this pilot study we found that TPA led to changes in MRI based resting state networks and associated functional outcome. Correlations were found between perfusion, functional connectivity and NIHSS. This suggests that the improvement of resting state network means improved efficiency of brain activity indicated by functional outcome and may be a potential predictive MRI biomarker for TPA response. A larger study is needed to verify this finding.

scholarly journals Exploring the potential value of miR-148b-3p, miR-151b and miR-27b-3p as biomarkers in acute ischemic stroke

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiuli Cheng ◽  
Pengcheng Kan ◽  
Zhuolin Ma ◽  
Yaru Wang ◽  
Wen Song ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Acute Ischemic Stroke ◽  
Roc Curve ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Healthy Controls ◽  
Insulin Like Growth Factor ◽  
Stroke Patients ◽  
Diagnostic Biomarkers

Cerebrovascular disease is the main cause of death in the world. Here, we explored whether circulating serum miR-148b-3p, miR-151b and miR-27b-3p could be as potential diagnostic biomarkers for diagnosing acute ischemic stroke. Seventy-seven IS patients and forty-two healthy controls matched for age and sex were enrolled in the present study. Blood samples were drawn from IS patients within the 24 h. The correlation analysis was performed by Spearman. The ability to distinguish patients from healthy controls was determined by receiver operating characteristic (ROC) curve. The expression of circulating serum miR-148b-3p was significantly decreased, whereas miR-151b and miR-27b-3p were elevated significantly compared with controls. ROC analysis showed area under the ROC curve (AUC) of miR-148b-3p, miR-151b and miR-27b-3p to be 0.6647, 0.6852 and 0.6657, respectively. While the AUC increased to 0.8103 for the combination of miR-148b-3p and miR-27b-3p. Blood miR-151b level was negatively correlated with insulin-like growth factor-1 (IGF-1), and miR-27b-3p level was negatively correlated with IGF-1 and insulin-like growth factor binding protein-3, respectively. Our findings suggest that miR-148b-3p, miR-151b and miR-27b-3p may serve as blood-based biomarkers for diagnosing ischemic stroke patients, and the combination of miR-148b-3p and miR-27b-3p may be more powerful.

scholarly journals Effect of Integrated Cognitive Therapy on Hippocampal Functional Connectivity Patterns in Stroke Patients with Cognitive Dysfunction: A Resting-State fMRI Study

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Shanli Yang ◽  
Cai Jiang ◽  
Haicheng Ye ◽  
Jing Tao ◽  
Jia Huang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Connectivity ◽  
Cognitive Therapy ◽  
Resting State ◽  
Insular Cortex ◽  
Resting State Fmri ◽  
Compensatory Mechanism ◽  
Seed Region ◽  
Stroke Patients ◽  
Cognitive Improvement

Objective. This study aimed to identify abnormal hippocampal functional connectivity (FC) following ischemic stroke using resting-state fMRI. We also explored whether abnormal hippocampal FC could be modulated by integrated cognitive therapy and tested whether these alterations were associated with cognitive performance.Methods. 18 right-handed cognitively impaired ischemic stroke patients and 18 healty control (HC) subjects were included in this study. Stroke subjects were scanned at baseline and after integrated cognitive therapy, while HCs were only scanned at baseline, to identify regions that show significant correlations with the seed region. Behavioral and cognitive assessments were obtained before each scan.Results. During the resting state, we found abnormal hippocampal FC associated with temporal regions, insular cortex, cerebellum, and prefrontal cortex in stroke patients compared to HCs. After integrated cognitive therapy, however, the stroke group showed increased hippocampal FC mainly located in the prefrontal gyrus and the default mode network (DMN). Altered hippocampal FC was associated with cognitive improvement.Conclusion. Resting-state fMRI may provide novel insight into the study of functional networks in the brain after stroke. Furthermore, altered hippocampal FC may be a compensatory mechanism for cognitive recovery after ischemic stroke.

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