The Clustering Analysis of Time Properties in Patients With Cerebral Small Vessel Disease: A Dynamic Connectivity Study

Front Neurol. 2022 Jun 20:13:913241. doi: 10.3389/fneur.2022.913241. eCollection 2022.

Abstract

Purpose: This study aimed to investigate the dynamic functional connectivity (DFC) pattern in cerebral small vessel disease (CSVD) and explore the relationships between DFC temporal properties and cognitive impairment in CSVD.

Methods: Functional data were collected from 67 CSVD patients, including 35 patients with subcortical vascular cognitive impairment (SVCI) and 32 cognitively unimpaired (CU) patients, as well as 35 healthy controls (HCs). The DFC properties were estimated by k-means clustering analysis. DFC strength analysis was used to explore the regional functional alterations between CSVD patients and HCs. Correlation analysis was used for DFC properties with cognition and SVD scores, respectively.

Results: The DFC analysis showed three distinct connectivity states (state I: sparsely connected, state II: strongly connected, state III: intermediate pattern). Compared to HCs, CSVD patients exhibited an increased proportion in state I and decreased proportion in state II. Besides, CSVD patients dwelled longer in state I while dwelled shorter in state II. CSVD subgroup analyses showed that state I frequently occurred and dwelled longer in SVCI compared with CSVD-CU. Also, the internetwork (frontal-parietal lobe, frontal-occipital lobe) and intranetwork (frontal lobe, occipital lobe) functional activities were obviously decreased in CSVD. Furthermore, the fractional windows and mean dwell time (MDT) in state I were negatively correlated with cognition in CSVD but opposite to cognition in state II.

Conclusion: Patients with CSVD accounted for a higher proportion and dwelled longer mean time in the sparsely connected state, while presented lower proportion and shorter mean dwell time in the strongly connected state, which was more prominent in SVCI. The changes in the DFC are associated with altered cognition in CSVD. This study provides a better explanation of the potential mechanism of CSVD patients with cognitive impairment from the perspective of DFC.

Keywords: cerebral small vessel disease; clustering analysis; cognitive impairment; dynamic functional connectivity; sliding window.