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White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective.

Abnormal functional connectivity density in patients with ischemic white matter lesions