Differentially disrupted functional connectivity in posteromedial cortical subregions in Alzheimer's disease

Neuroimaging studies have demonstrated that patients with Alzheimer's disease (AD) have remarkable focal grey matter loss and hypometabolism in the posteromedial cortex (PMC), which is composed of the precuneus and posterior cingulate cortex, suggesting an important association of the PMC with AD pathophysiology. Studies have also shown that the PMC is a structurally and functionally heterogeneous structure containing various subregions with distinct connectivity profiles. However, whether these PMC subregions show differentially disrupted connectivity patterns in AD remains largely unknown. Here, we addressed this issue by collecting resting-state functional MRI data from 32 AD patients and 38 healthy controls. We automatically identified the PMC subregions using a graph-based module detection algorithm and then mapped the whole-brain functional connectivity pattern of each subregion. The functional connectivity analysis was followed by a hierarchical clustering analysis to classify each subregion. Three distinct spatial connectivity patterns were observed across the PMC subregions: the anterior dorsal zone was functionally connected with the sensorimotor cortex; the posterior dorsal zone was functionally connected with the frontoparietal cortex; and the central and ventral zones were functionally connected with the default-mode regions. Group comparison analysis revealed that all three functional systems were significantly disrupted in the AD patients compared to the controls and these disruptions were positively correlated with the patients' cognitive performance. Collectively, we showed that the subregions of the PMC exhibit differentially disrupted neuronal circuitry in AD patients, which provides new insight into the functional neuroanatomy of the human PMC and the alterations that may be relevant to disease.