Neural Correlates and Adaptive Mechanisms in Vascular Cognitive Impairment: Exploration of a Structure-Function Coupling Network

Abstract

Background: Cerebral small vessel disease exacerbates cognitive decline, yet the structural-functional coupling mechanisms in vascular cognitive impairment (VCI) remain unclear.

Methods: This study included 121 participants, with 68 individuals with VCI and 53 healthy controls. Participants underwent neuropsychological assessments and multimodal imaging. We compared white matter integrity, structural network topology, and functional network topology between groups, exploring the relationship between structure-function coupling and cognitive function. Family-wise error (FWE) correction was applied to account for multiple comparisons.

Results: VCI participants showed reduced fractional anisotropy and increased mean and radial diffusivity in white matter. Structural network analysis revealed lower global and local efficiency, reduced small-world properties, and increased characteristic path length. Nodal properties, particularly in key regions of the default mode and visual networks, were significantly altered in VCI participants. While no significant differences were observed in functional network topology, VCI participants exhibited enhanced structure-function coupling in critical nodes of the default mode and visual networks. This enhancement correlated with memory function and information processing speed in the temporal calcarine, insula, occipital, and lingual regions.

Conclusions: The study identifies disrupted brain networks and enhanced compensatory mechanisms in VCI, offering insights into neuroplasticity in VCI and contributing to dementia prevention strategies.

Keywords: function network; structure network; structure–function coupling; vascular cognitive impairment; white matter hyperintensity.

FIGURE 1

Enrollment and disposition of participants. Abbreviations: HC, healthy control; MRI, magnetic resonance imaging; N, number; VCI, vascular cognitive impairment.

FIGURE 2

Group differences of diffusion tensor metrics for comparison between vascular cognitive impairment (VCI) participants and healthy controls (HCs). Abbreviations: AD: axial diffusivity; FA: fractional anisotropy; MD: mean diffusivity; RD: radial diffusivity.

FIGURE 3

Group differences in structural network topological properties between vascular cognitive impairment (VCI) participants and healthy controls (HCs). (A) Box‐and‐whisker plots illustrating the area under the curve (AUC) parameters of global efficiency (Eglob), local efficiency (Eloc), clustering coefficient (Cp), characteristic path length (Lp), and small‐worldness (Sigma) for VCI participants and healthy controls. Means and standard deviations are depicted. (B) Group differences in degree, efficiency, and shortest path at the nodal level. Insignificant nodes are shown as green spheres, whereas blue (VCIHC) spheres denote significant differences after FWE correction, with regions labeled where p < 0.001. The size of the significant nodes reflects the effect sizes of group differences. Abbreviations: AMYG, amygdala; CAL, calcarine cortex; CUN, cuneus; L, left; MOG, middle occipital gyrus; PCG, posterior cingulate gyrus; PCUN, precuneus; PoCG, postcentral gyrus; PreCG, precentral gyrus; PUT, putamen; R, right; SPG, superior parietal gyrus.

FIGURE 4

Group differences in functional network topological properties between vascular cognitive impairment (VCI) participants and healthy controls (HCs). Abbreviations: aCp, area under the curve for clustering coefficient; AEglob, area under the curve for global efficiency; aEloc, area under the curve for local efficiency; aLp, area under the curve for characteristic path length; aSigma, area under the curve for sigma.

FIGURE 5

Structure–function coupling. (A) Scatter plot of resting‐state functional connectivity (rsFC) against structural connectivity (SC) at high resolution for healthy control 001 (HC 001), showing edges with nonzero SC. (B) Sparse structural brain network connectivity map and resting‐state functional network connectivity map for HC participant 001 (sparsity 0.01–0.4, step 0.01). (C) Insignificant nodes are shown as green spheres, while red spheres (VCI>HC) denote significant differences after FWE correction, with regions labeled where p < 0.0001. Abbreviations: CAL, calcarine cortex; CUN, cuneus; FFG, fusiform gyrus; HIP, hippocampus; INS, insula; IOG, inferior occipital gyrus; ITG, inferior temporal gyrus; L, left; LING, lingual gyrus; MTG, middle temporal gyrus; PCUN, right precuneus; STG, superior temporal gyrus; MFG, middle frontal gyrus; ORBsup, superior orbital gyrus, PCL, paracentral lobule; PoCG, postcentral gyrus; PreCG, precentral gyrus; R, right; SFGdor, dorsolateral superior frontal gyrus; SMA, supplementary motor area; SOG, superior occipital gyrus.

FIGURE 6

Circos diagram of structural–functional coupling and cognitive function. The color intensity of the lines represents the correlation coefficient value, with darker lines indicating a stronger correlation between the brain region and the cognitive function at the respective node. The size of the node's circle corresponds to the number of connections, indicating the degree of influence of the node. Abbreviations: AVLT, Auditory Verbal Learning Test; AVLT_N5, Auditory Verbal Learning Test, Long‐Term Delay Recall; BNT, Boston Naming Test; Inf, inferior; L, left; Mid, middle; R, right; SDMT correct, Symbol Digit Modalities Test, correct number; STT_B, Shape Trails Test, part B; Sup, Superior.