Disconnection of Network Hubs Underlying the Executive Function Deficit in Patients with Ischemic Leukoaraiosis

Background: Cognitive impairment is the most common clinical manifestation of ischemic leukoaraiosis (ILA), but the underlying neurobiological pathways have not been well elucidated. Recently, it was thought that ILA is a "disconnection syndrome". Disorganized brain connectome were considered the key neuropathology underlying cognitive deficits in ILA patients. Objective: We aimed to detect the disruption of network hubs in ILA patients using a newanalytical method called voxel-based eigenvector centrality (EC) mapping. Methods: Subjects with moderate to severe white matters hyperintensities (Fazekas score >= 3) and healthy controls (HCs) (Fazekas score = 0) were included in the study. The resting-state functional magnetic resonance imaging and the EC mapping approach were performed to explore the alteration of whole-brain network connectivity in ILA patients. Results: Relative to the HCs, the ILA patients exhibited poorer cognitive performance in episodic memory, information processing speed, and executive function (all p(s) < 0.0125). Additionally, compared with HCs, the ILA patients had lower functional connectivity (i.e., EC values) in the medial parts of default-mode network (i.e., bilateral posterior cingulate gyrus and ventral medial prefrontal cortex [vMPFC]). Intriguingly, the functional connectivity strength at the right vMPFC was positively correlated with executive function deficit in the ILA patients. Conclusion: The findings suggested disorganization of the hierarchy of the default-mode regions within the whole-brain network in patients with ILA and advanced our understanding of the neurobiological mechanism underlying executive function deficit in ILA.