White matter hyperintensity-associated structural disconnection, resting state functional connectivity, and cognitive control in older adults

White matter hyperintensities (WMH) are linked to cognitive control; however, the structural and functional mechanisms are largely unknown. We investigated the relationship between WMH-associated disruptions of structural connectivity, resting state functional connectivity (RSFC), and cognitive control in older adults. Fifty-eight cognitively-healthy older adults completed cognitive control tasks, structural MRI, and resting state fMRI scans. We estimated inferred, WMH-related disruptions in structural connectivity between pairs of subcortical and cortical regions by overlaying each participant’s WMH mask on a normative tractogram dataset. For region-pairs in which structural disconnection was associated with cognitive control, we calculated RSFC between nodes in those same regions. WMH-related structural disconnection and RSFC in the cognitive control network and default mode network were both associated with poorer cognitive inhibition. These regionally-specific, WMH-related structural and functional changes were more strongly associated with cognitive inhibition compared to standard rating of WMH burden. Our findings highlight the role of circuit-level disruptions to the cognitive control network and default mode network that are related to WMH and impact cognitive control in aging.