White matter hyper-intensities (WMH) is considered as an important source of morbidity associated with dementia, stroke and increased mortality risk. Previous studies have suggested that WMH always leads to the decline of information processing speed, which have an impact on activities of daily living. Current hypothesis is that the dysfunctions caused by WMH is the result of “disconnection”, while the connection between the structural and functional alteration has not been fully investigated. We aimed to explore the underlying pathway of information processing speed decline via combining the spatial distribution of WMH, microstructural changes based tractography and cortical activity alterations. The results from different modalities converged in the occipital lobe with precise spatial overlappings. Results show regional WMH may indicate disrupted tract integrity and cause altered brain activities, leading to impaired function. This WMH-tract-function-behavior link is critical for WMH induced dysfunctions and treatment strategies.