Both episodic memory and executive function are impaired in amnestic mild cognitive impairment (aMCI) subjects, but it is unclear if these impairments are independent or interactive. The present study aimed to explore the relationship between episodic memory deficits and executive function deficits, and the underlying functional mechanisms in aMCI subjects. Thirty-one aMCI subjects and 27 healthy subjects underwent neuropsychological tests and multimodal magnetic resonance imaging (MRI) scans. Hippocampal networks and medial prefrontal cortex (MPFC) networks were identified based on resting-sate functional MRI (fMRI) data. AMCI subjects displayed lower episodic memory scores and executive function scores than control subjects, and the episodic memory scores were positively correlated with the executive function scores in aMCI subjects. Brain network analyses showed an interaction between the hippocampal networks and the MPFC networks, and the interaction was significantly associated with the episodic memory scores and the executive function scores. Notably, aMCI subjects displayed higher functional connectivity (FC) of the right hippocampal network with the right prefrontal cortex than did control subjects, but this difference disappeared when controlling for the MPFC networks. Furthermore, the effects of the MPFC networks on the hippocampal networks were significantly associated with the episodic memory scores in aMCI subjects. The present findings suggested that the episodic memory deficits in aMCI subjects could be partially underpinned by the modulation of the MPFC networks on the hippocampal networks.

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