Impaired dynamic profile of brain recurring functional connectivity states in Alzheimer’s disease

Abstract

Up to now, disrupted functional organization of the brain in Alzheimer’s disease (AD) has mostly been examined by assessing “static” functional connectivity (FC). However, recent studies have provided clear evidence that brain FC exhibits intrinsic spatiotemporal “dynamic” organization also being significantly affected in AD. However, inconsistency in former studies is a motivation for further investigation of impaired dynamic profile of brain FC networks in Alzheimer’s disease._In this work, we identified recurring FC states during rest (eyes-open) in 24 AD patients and 37 healthy controls (HC) by combining sliding window-based method (examining dynamic FC) and k-means clustering algorithm (identifying recurring FC states over time). To define the optimum number of recurring FC states in k-means algorithm, we employed non-supervised validity criteria such as silhouette value and Dunn index over bootstrap samples. Then, we examined differences in dynamic properties of recurring FC states including probability of occurrence, lifetime and switching profile between groups. Afterward, association between impaired dynamic profile of recurring FC states and cognitive performance was assessed in AD patients. Our findings revealed three recurring FC states and among them, FC state with the most significant differences in probability of occurrence (corrected p-value < 0.0001) included brain regions involved in default mode, frontoparietal and salience networks. This recurring FC state occurred significantly less and lasted shorter in patients with AD than in the HC. Further, the probability of occurrence in this recurring FC state significantly correlated positively with cognitive decline in patients with AD. Our findings suggest more decreased in cognitive performance in patients with AD associated with more reduced ability of AD patients to access clinically relevant impaired brain FC networks. Impaired dynamic profile of recurring FC states in AD provide greater understanding of AD’s pathophysiology.