Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer’s Disease: A Resting-State fMRI Study

The hippocampus is generally reported as one of the regions most impacted by Alzheimer’s disease (AD) and is closely associated with memory function and orientation. Undirected functional connectivity (FC) alterations occur in patients with mild cognitive impairment (MCI) and AD, and these alterations have been the subject of many studies. However, abnormal patterns of directed FC remain poorly understood. In this study, to identify changes in directed FC between the hippocampus and other brain regions, Granger causality analysis (GCA) based on voxels was applied to resting-state functional magnetic resonance imaging (rs-fMRI) data from 29 AD, 65 MCI, and 30 normal control (NC) subjects. The results showed significant differences in the patterns of directed FC among the three groups. There were fewer brain regions showing changes in directed FC with the hippocampus in the MCI group than the NC group, and these regions were mainly located in the temporal lobe, frontal lobe, and cingulate cortex. However, regarding the abnormalities in directed FC in the AD group, the number of affected voxels was greater, the size of the clusters was larger, and the distribution was wider. Most of the abnormal connections were unidirectional and showed hemispheric asymmetry. In addition, we also investigated the correlations between the abnormal directional FCs and cognitive and clinical measurement scores in the three groups and found that some of them were significantly correlated. This study revealed abnormalities in the transmission and reception of information in the hippocampus of MCI and AD patients and offer insight into the neurophysiological mechanisms underlying MCI and AD.