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

Article type: Research Article

Authors: Wang, Mengxue^{a; 1} | Zhao, Guofeng^{b; c; 1} | Jiang, Ying^d | Lu, Tong^e | Wang, Yanjuan^a | Zhu, Yixin^a | Zhang, Zhengsheng^a | Xie, Chunming^a | Wang, Zan^{a; *} | Ren, Qingguo^{a; *}

Affiliations: [a] Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China | [b] Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China | [c] Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, China | [d] Department of Neurology, The 962nd Hospital of the PLA Joint Logistic Support Force, Harbin, China | [e] Department of Radiology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China

Correspondence: [*] Correspondence to: Zan Wang and Qingguo Ren, Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China. E-mail: ujs_nyingxiang0402@126.com (Z. Wang) and E-mail: renqingguo1976@163.com (Q. Ren).

Note: [1] These authors contributed equally to this work.

Abstract: 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 new analytical 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 ps < 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.

Keywords: Brain connectome, default-mode network, eigenvector centrality mapping, executive function, ischemic leukoaraiosis, resting-state fMRI

DOI: 10.3233/JAD-230048

Journal: Journal of Alzheimer's Disease, vol. 94, no. 4, pp. 1577-1586, 2023