Resting-State Functional Connectivity Alterations in Individuals With White Matter Hyperintensities: A...

White-matter hyperintensities (WMHs) are a signature feature of cerebral small-vessel disease and are associated with cognitive decline. This study used network-based statistics (NBS) to investigate global functional network changes and their association with cognitive function in individuals with WMHs.

The Montreal Cognitive Assessment (MoCA) was administered to 33 individuals with WMHs and 34 healthy controls. Whole-brain resting-state functional-connectivity (RSFC) differences were analyzed using NBS on resting-state functional Magnetic Resonance Imaging data. Significant connectivity of modular changes within and between networks was examined, and the relationship between MoCA and RSFC was analyzed. Support vector machine (SVM) models were used to evaluate the potential of functional networks as a supplement to structural imaging and a sensitive subclinical indicator.

Individuals with WMHs exhibited significantly lower MoCA scores than did healthy controls. Inter-regional RSFC analysis revealed reduced connectivity across some networks, including the Default Mode Network-Sensorimotor Network (DMN-SMN), DMN-Cingulo-Opercular Network (DMN-CON), and CON-Cerebellar Network (CON-CER). The SVM models demonstrated robust classification performance, with areas under the curve (AUC) of 0.864 ± 0.155 for DMN-SMN, 0.838 ± 0.175 for DMN-CON, and 0.821 ± 0.167 for CON-CER. Global RSFC strength and modular RSFC strength were positively correlated with MoCA scores.

WMHs are associated with widespread RSFC alterations, especially in networks involved in cognition and motor control; these differences may contribute to cognitive decline in WMHs and serve as potential biomarkers for early diagnosis and intervention.