Equalization of Brain State Occupancy Accompanies Cognitive Impairment in Cerebral Small Vessel Disease

Schlemm, Eckhard; Frey, Benedikt M.; Mayer, Christine M.; Petersen, Marvin; Fiehler, Jens; Hanning, Uta; Kühn, Simone; Twerenbold, Raphael; Gallinat, Jürgen; Gerloff, Christian; Thomalla, Götz; Cheng, Bastian

doi:10.1016/j.biopsych.2022.03.019

Cited by 9 publications

(6 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AUD, auditory; BG, basal ganglia; CB, cerebellar; CEN, cognitive executive; DMN, default mode; SMN, sensorimotor; VIS, visual Regarding the temporal properties of DFC, our study found that the CSVD group had significantly fewer fractional windows and shorter mean dwell times in state 3 than the NC group, indicating the disconnection of intra-network FC and the reduced integration of inter-network FC between the SMN and VIS network in the CSVD group. A recent study showed that the increase in WMH burden in patients with CSVD was associated with a decrease in time spent in highoccupancy states [45]. Despite slight differences in inclusion criteria, the results showed similarities.…”

Section: Discussionmentioning

confidence: 94%

Alterations in Dynamic Functional Connectivity in Patients with Cerebral Small Vessel Disease

Chen

Zhu

et al. 2023

Transl. Stroke Res.

View full text Add to dashboard Cite

Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people’s health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks that represents a powerful tool for gaining novel insight into neurological diseases. To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function. We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI (rs-fMRI) with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the functional connectivity (FC) strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance. A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse FC both inter-network and intra-networks. Additionally, the CSVD group had a reduced number of windows and shorter mean dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state 2 and state 3 and between state 3 and state 4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a significant difference in the FC strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance. Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC alterations could help us to better understand the progressive dysfunction of networks in CSVD patients.

show abstract

Section: Discussionmentioning

confidence: 94%

Alterations in Dynamic Functional Connectivity in Patients with Cerebral Small Vessel Disease

Chen

Zhu

et al. 2023

Transl. Stroke Res.

View full text Add to dashboard Cite

show abstract

“…We provide evidence for the considerable role of WMH-related “covert” network effects as indicated previously in studies from smaller clinical or population-based studies. 8,44–46…”

Section: Discussionmentioning

confidence: 99%

Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients

Petersen,

Coenen,

DeCarli

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating cognitive health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. We propose that lesion network mapping (LNM), enabling the inference of brain networks disconnected by lesions, represents a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed this approach to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. Methods & results: We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity across 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. The capacity of total and regional WMH volumes and LNM scores in predicting cognitive function was compared using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention and executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater disruptive effects of WMH on regional connectivity, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Conclusion: WMH-related brain network disconnectivity significantly improves the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network effects, particularly in attention-related brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

show abstract

“…Executive functions include complete thinking and behavioral skills that assist with goal guidance, inference, planning, and synthesis, which is the typical cognitive deficiency pattern of WMHs (Prins et al, 2005). Recently, correlations between executive dysfunction and WMHs in the region-specific periventricular lesions have been confirmed (Schlemm et al, 2022). The mechanisms underlying multidimensional executive functions are interconnected and integrated across the whole brain.…”

Section: Correlation With Clinical Measuresmentioning

confidence: 99%

Altered dynamic functional network connectivity and topological organization variance in patients with white matter hyperintensities

Huang,

Zhou,

Ren

et al. 2023

J of Neuroscience Research

View full text Add to dashboard Cite

White matter hyperintensities (WMHs) of presumed vascular origin are important imaging biomarkers of cerebral small vessel disease (CSVD). Previous studies have verified abnormal functional brain networks in CSVD. However, most of these studies rely on static functional connectivity, and only a few focus on the varying severity of the WMHs. Hence, our study primarily explored the disrupted dynamic functional network connectivity (dFNC) and topological organization variance in patients with WMHs. This study included 38 patients with moderate WMHs, 47 with severe WMHs, and 68 healthy controls (HCs). Ten independent components were chosen using independent component analysis based on resting‐state functional magnetic resonance imaging. The dFNC of each participant was estimated using sliding windows and k‐means clustering. We identified three reproducible dFNC states. Among them, patients with WMHs had a significantly higher occurrence in the sparsely connected State 1, but a lower occurrence and shorter duration in the positive and stronger connected State 3. Regarding topological organization variance, patients with WMHs showed higher variance in local efficiency but not global efficiency compared to HCs. Among the WMH subgroups, patients with severe WMHs showed similar but more obvious alterations than those with moderate WMHs. These altered network characteristics indicated an imbalance between the functional segregation and integration of brain networks, which was correlated with global cognition, memory, executive functions, and visuospatial abilities. Our study confirmed aberrant dFNC state metrics and topological organization variance in patients with moderate‐to‐severe WMHs; thus, it might provide a new pathway for exploring the pathogenesis of cognitive impairment.

show abstract

Equalization of Brain State Occupancy Accompanies Cognitive Impairment in Cerebral Small Vessel Disease

Cited by 9 publications

References 113 publications

Alterations in Dynamic Functional Connectivity in Patients with Cerebral Small Vessel Disease

Alterations in Dynamic Functional Connectivity in Patients with Cerebral Small Vessel Disease

Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients

Altered dynamic functional network connectivity and topological organization variance in patients with white matter hyperintensities

Contact Info

Product

Resources

About