Primary Disruption of the Memory-Related Subsystems of the Default Mode Network in Alzheimer’s Disease: Resting-State Functional Connectivity MRI Study

Abstract

Background: Recent studies have indicated that the default mode network (DMN) comprises at least three subsystems: The medial temporal lobe (MTL) and dorsal medial prefrontal cortex (DMPFC) subsystems and a core comprising the anterior MPFC (aMPFC) and posterior cingulate cortex (PCC). Additionally, the disruption of the DMN is related to Alzheimer’s disease (AD). However, little is known regarding the changes in these subsystems in AD, a progressive disease characterized by memory impairment. Here, we performed a resting-state functional connectivity (FC) analysis to test our hypothesis that the memory-related MTL subsystem was predominantly disrupted in AD. Method: To reveal specific subsystem changes, we calculated the strength and number of FCS in the DMN intra- and inter-subsystems across individuals and compared the FC of the two groups. To further examine which pairs of brain regional functional connections contributed to the subsystem alterations, correlation coefficients between any two brain regions in the DMN were compared across groups. Additionally, to identify which regions made the strongest contributions to the subsystem changes, we calculated the regional FC strength (FCS), which was compared across groups. Results: For the intra-subsystem, decreased FC number and strength occurred in the MTL subsystem of AD patients but not in the DMPFC subsystem or core. For the inter-subsystems, the AD group showed decreased FCS and number between the MTL subsystem and PCC and a decreased number between the PCC and DMPFC subsystem. Decreased inter-regional FCS were found within the MTL subsystem in AD patients relative to controls: The posterior inferior parietal lobule (pIPL) showed decreased FC with the hippocampal formation (HF), parahippocampal cortex (PHC) and ventral MPFC (vMPFC). Decreased inter-regional FCS of the inter-subsystems were also found in AD patients: The HF and/or PHC showed decreased FC with dMPFC and TPJ, located in the DMPFC subsystem, and with PCC. AD patients also showed decreased FC between the PCC and TLC of the dMPFC subsystem. Furthermore, the HF and PHC in the MTL subsystem showed decreased regional FCS. Conclusion: Decreased intrinsic FC was mainly associated with the MTL subsystem of the AD group, suggesting that the MTL subsystem is predominantly disrupted.