Cerebrovascular reactivity in white matter related to global white matter hyperintensity burden and functional connectivity

Motivation: White matter hyperintensity (WMH) burden is associated with vascular risk and impaired default mode network (DMN) function in aging. However, mechanisms underlying these relationships remain unclear. Goal(s): Cerebrovascular reactivity (CVR), an indicator of vascular reserve, could provide mechanistic insight into how vascular injury in white matter affects functional connectivity (FC). Approach: We leverage a novel CVR technique based on resting-state functional MRI to investigate how vascular injury (WMH) affects white matter cerebrovascular function and gray matter FC. Results: Global WMH burden is negatively associated with relative CVR in the cingulum. Furthermore, cingulum relative CVR is positively associated with FC within the DMN. Impact: This study provides mechanistic insight into how WMH burden affects cerebrovascular reactivity (measured by resting-state functional MRI) and functional connectivity in brain injury. This knowledge can help identify brain networks vulnerable to cerebrovascular injury and inform prevention of cognitive decline.