Multimodal MRI Reveals Stage-Specific Reorganization of Structure-Function Coupling from Compensatory to Decoupled States in Cerebral Small Vessel Disease.

Authors

Tianqi Wang, Shuai Lin, Chang Xu, Yue Chen, Ying Sui, Jiali Sun, Ruotong Wang, Heyang Chen, Jianxiu Lian, Wei Wang

Published in

Academic radiology. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Cerebral small vessel disease (CSVD) affects white matter integrity and can alter the brain's network architecture. However, the relationship between structural and functional connectivity in CSVD remains underexplored. This study aims to investigate the differences in topological properties of structural and functional brain networks across CSVD burden groups.
This cross-sectional study utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu), concentrating on participants who had both DTI and resting-state fMRI data. Participants were classified into non-CSVD (CSVD-n), mild CSVD (CSVD-m), or severe CSVD (CSVD-s) groups based on a CSVD burden score ranging from zero to four. Structural networks were reconstructed from DTI data using deterministic tractography, while functional networks were derived from resting-state fMRI data through Pearson's correlation of regional time series. Graph theoretical analyses were conducted using GRETNA in MATLAB to calculate global and nodal metrics, as well as structure-function coupling indices. Group comparisons were performed using one-way ANOVA (one-way analysis of variance), with age, sex, and education as covariates. Statistical significance was assessed at a two-tailed p < 0.05, adjusted for multiple comparisons across nodes and networks using false discovery rate (FDR) correction.
The study included 280 participants (mean 75.0±7.9y, median 76y; 49.6% female). The participants were divided into groups: CSVD‑n (118, 42.1%), CSVD‑m (80, 28.6%), and CSVD‑s (82, 29.3%). Analysis of structural networks revealed that CSVD‑s exhibited reduced global/local efficiency (7.42±2.63 vs. 8.42±2.75, p = 0.03; 16.00±4.77 vs. 17.83±5.16, p = 0.02) and increased path length (0.15±0.04 vs. 0.13±0.04, p = 0.003). Nodal damage was observed in the left hippocampus in CSVD‑m (p = 0.0008) and was widespread in CSVD‑s (all p < 0.001). In terms of functional networks, no global differences were found (all p > 0.05); however, CSVD‑s exhibited nodal changes in the cingulate/Heschl gyrus (p < 0.001). Regarding coupling, CSVD‑m showed increased coupling in the insula/orbitofrontal regions (p = 0.002-0.041) and decreased coupling in the pallidum (p = 0.026). Conversely, CSVD‑s demonstrated increased coupling in the olfactory/occipital/temporal regions (p = 0.001-0.023) and decreased coupling in the rolandic operculum (p = 0.019) and hippocampus (compared to CSVD‑m, p = 0.009). Furthermore, left insular coupling was correlated with MoCA (r=-0.245, p = 0.015).
In the mild CSVD group, researchers observed increased coupling in regions such as the insula and orbitofrontal cortex. In contrast, the severe CSVD group exhibited widespread structural network differences, decreased coupling in the hippocampus and rolandic operculum, and functional nodal alterations. These cross-sectional comparisons among CSVD burden groups reveal a pattern of differences consistent with stage-like progression. However, causality cannot be inferred from this cross-sectional design.

PMID:
42448482
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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