Disrupted topological organization of resting-state functional brain networks in cerebral small vessel disease

Abstract

We aimed to investigate alterations in functional brain networks and assess the relationship between functional impairment and topological network changes in cerebral small vessel disease (CSVD) patients with and without cerebral microbleeds (CMBs). We constructed individual whole-brain, region of interest (ROI) level functional connectivity (FC) networks for 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n), and 36 healthy controls (HCs). Then, we used graph theory analysis to investigate the global and nodal topological disruptions between groups and relate network topological alterations to clinical parameters. We found that both the CSVD and control groups showed efficient small-world organization in FC networks. However, compared to CSVD-n patients and controls, CSVD-c patients exhibited a significantly decreased clustering coefficient, global efficiency, and local efficiency and an increased shortest path length, indicating a disrupted balance between local specialization and global integration in FC networks. Although both the CSVD and control groups showed highly similar hub distributions, the CSVD-c group exhibited significantly altered nodal betweenness centrality (BC), mainly distributed in the default mode network (DMN), attention, and visual functional areas. There were almost no global or regional alterations between CSVD-n patients and controls. Furthermore, the altered nodal BC of the right anterior/posterior cingulate gyrus and left cuneus were significantly correlated with cognitive parameters in CSVD patients. These results suggest that CSVD patients with and without CMBs had segregated disruptions in the topological organization of the intrinsic functional brain network. This study advances our current understanding of the pathophysiological mechanisms underlying CSVD.

Keywords: cerebral microbleeds; cerebral small vessel disease; functional connectivity; graph theory; topological organization.

FIGURE 1

Differences in global topological properties of functional networks among the three groups. Data points marked with a star indicate significant (p < 0.05, ANOVA with LSD post hoc test) intergroup differences in the global network metric under a corresponding sparsity threshold

FIGURE 2

Hub region distributions of the functional networks for both groups. The hub nodes are shown with different node sizes, indicating their nodal betweenness centrality values. The brain graphs were visualized by using BrainNet Viewer software (http://www.nitrc.org/projects/bnv/). For the abbreviations of the nodes, see Table 1

FIGURE 3

The differences in nodal betweenness centrality of the functional networks across the CSVD‐c, CSVD‐n, and HC groups. The disrupted nodes with significantly decreased or increased nodal betweenness centrality are shown in blue or red, and the scaled node sizes indicate the F values of ANOVA. For the abbreviations of the nodes, see Table 1

FIGURE 4

Correlations between nodal topological properties and clinical parameters. Of note, the coordinate values of both the X axis (clinical parameter) and Y axis (nodal BC) do not reflect the initial values of these variables when considering age, sex and mean FD as covariates. For the abbreviations of the nodes, see Tables 1 and 3