Disrupted Causal Connectivity Anchored in the Posterior Cingulate Cortex in Amnestic Mild Cognitive Impairment

Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal cognitive aging and Alzheimer's disease. Previous studies have found that neuronal activity and functional connectivity impaired in many functional networks, especially in the default mode network (DMN), which is related to significantly impaired cognitive and memory functions in aMCI patients. However, few studies have focused on the effective connectivity of the DMN and its subsystems in aMCI patients. The posterior cingulate cortex (PCC) is considered a crucial region in connectivity of the DMN and its key subsystem. In this study, using the coefficient Granger causality analysis approach and using the PCC as the region of interest, we explored changes in the DMN and its subsystems in effective connectivity with other brain regions as well as in correlations among them in 16 aMCI patients and 15 age-matched cognitively normal elderly. Results showed decreased effective connectivity from PCC to whole brain in the left prefrontal cortex, the left medial temporal lobe (MTL), the left fusiform gyrus (FG), and the left cerebellar hemisphere, meanwhile, right temporal lobe showed increased effective connectivity from PCC to the whole brain in aMCI patients compared with normal control. In addition, compared with the normal controls, increased effective connectivity of the whole brain to the PCC in aMCI patients was found in the right thalamus, left medial temporal lobe, left FG, and left cerebellar hemisphere. Compared with the normal controls, no reduced effective connectivity was found in any brain regions from the whole brain to the PCC in aMCI patients. The reduced effective connectivity of the PCC to left MTL showed negative correlation trend with neuropsychological tests (Auditory Verbal Learning Test-immediate recall and clock drawing test) in aMCI patients. Our study shows that aMCI patients have abnormalities in effective connectivity within the PCC-centered DMN network and its posterior subsystems as well as in the cerebellar hemisphere and thalamus. Abnormal integration of networks may be related to cognitive and memory impairment and compensation mechanisms in aMCI patients.