State-based functional connectivity changes associate with cognitive decline in amnestic mild cognitive impairment...

Episodic memory (EM) dysfunction is a central characteristic of amnestic mild cognitive impairment (aMCI) subjects, and has a high risk of converting to Alzheimer's disease (AD). However, it is unknown how the EM network is modulated when a situation is switched. Twenty-six aMCI and twenty-two cognitively normal (CN) subjects were enrolled in this study. All of the subjects completed multi-dimensional neuropsychological tests and underwent functional magnetic resonance imaging scans during a resting-state and an episodic memory retrieval task state. The EM network was constructed using a seed-based functional connectivity (FC) approach. AMCI subjects showed poorer cognitive performances in the episodic memory and executive function. We demonstrated that connectivity of the left posterior parahippocampal gyrus (LpPHG) connected to the left ventral medial prefrontal cortex and the right postcentral gyrus (RPCG) was significantly decreased in aMCI subjects compared to CN subjects. Meanwhile, there was increased connectivity of the LpPHG to the right dorsal medial prefrontal cortex (RDMPFC), RPCG, left inferior parietal cortex, and bilateral superior parietal lobe in all of the subjects that changed from a resting-state to a task-state. Interestingly, the changed LpPHG-RDMPFC connectivity strength was significantly correlated with EM scores and executive function in the aMCI subjects. As a result, general brain regions are functionally organized and integrated into the EM network, and this strongly suggests that more cognitive resources are mobilized to meet the challenge of cognitive demand in the task state. These findings extend our understanding of the underlying mechanisms of EM deficits in aMCI subjects.