Large-scale functional network connectivity mediate the associations of white matter lesions with executive functions and information processing speed in asymptomatic cerebral small vessels diseases.

Objective: To examine the role of the large-scale functional network connectivity between white matter lesions (WMLs) and cognitive behaviors in patients of asymptomatic cerebral small vascular diseases (CSVD).

Methods: The study sample consisted of 211 asymptomatic CSVD patients with WMLs. Large-scale internetwork and intranetwork functional connectivity (FC) were calculated using a combination of resting-state functional MRI data and independent component analysis. Neuropsychological tests involve cognitive functions were also measured. Then, potential correlations between WMLs, functional network connectivity and cognitive behaviors were tested. Mediation analysis was used to explore the role of functional network connectivity between WMLs and cognitive behaviors.

Results: We successfully identified fourteen meaningful resting-state functional networks. Internetwork FC between dorsal sensorimotor network (dSMN) and right frontoparietal network (rFPN), dSMN and left frontoparietal network (lFPN), auditory network (AN) and posterior default network (pDMN), AN and executive control network (ECN), ECN and salience network (SN), dorsal attention network (DAN) and ECN were significant correlated with volumes of WMLs. Executive function were associated with internetwork FC between AN and pDMN, ECN and SN. Moreover, internetwork FC between AN and pDMN, ECN and SN mediated the relations of WMLs with executive function (for AN and pDMN, indirect effect: -0.0371, 95% CI: -0.0829 to -0.0073; for ECN and SN, indirect effect: -0.03191, 95% CI: -0.0807 to -0.0047). Moreover, left inferior parietal lobule in rFPN, right precentral gyrus in anterior default network (aDMN), right paracentral lobue in pDMN and left precunues in ECN were related to volumes of WMLs. There is a significant association of WMLs with intranetwork FC in left precunues, which could mediate the link between WMLs and information processing speed (indirect effect: -0.0437, 95% CI: -0.1055 to -0.0081).

Conclusion: WMLs in asymptomatic CSVD patients may induce large-scale connectivity changes including the internetwork FC and intranetwork FC, which might further influence executive function and information processing speed.