Abstract

Most neuroimaging studies of resting state networks in amnesic mild cognitive impairment (aMCI) have concentrated on functional connectivity (FC) based on instantaneous correlation in a single network. The purpose of the current study was to investigate effective connectivity in aMCI patients based on Granger causality of four important networks at resting state derived from functional magnetic resonance imaging data – default mode network (DMN), hippocampal cortical memory network (HCMN), dorsal attention network (DAN) and fronto-parietal control network (FPCN). Structural and functional MRI data were collected from 16 aMCI patients and 16 age, gender-matched healthy controls. Correlation-purged Granger causality analysis was used, taking gray matter atrophy as covariates, to compare the group difference between aMCI patients and healthy controls. We found that the causal connectivity between networks in aMCI patients was significantly altered with both increases and decreases in the aMCI group as compared to healthy controls. Some alterations were significantly correlated with the disease severity as measured by mini-mental state examination (MMSE), and California verbal learning test (CVLT) scores. When the whole-brain signal averaged over the entire brain was used as a nuisance co-variate, the within-group maps were significantly altered while the between-group difference maps did not. These results suggest that the alterations in causal influences may be one of the possible underlying substrates of cognitive impairments in aMCI. The present study extends and complements previous FC studies and demonstrates the coexistence of causal disconnection and compensation in aMCI patients, and thus might provide insights into biological mechanism of the disease.

Highlights

  • Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide with symptoms of global cognitive decline, including progressive loss of memory, reasoning and language

  • There were no significant differences between Amnesic mild cognitive impairment (aMCI) patients and healthy controls in gender, age, and years of education, but the mini-mental state examination (MMSE), California verbal learning test (CVLT) and CDT scores were significantly different (P,0.05) between the two groups

  • The novelty of the present study lies in the fact that we have used directional connectivity methods to explore the underlying biological markers of MCI

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Summary

Introduction

Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide with symptoms of global cognitive decline, including progressive loss of memory, reasoning and language. Amnesic mild cognitive impairment (aMCI) is an intermediate state between healthy aging and AD, with a higher risk of developing dementia (rate of conversion of 10–15% per year) [2]. There has been much anatomical and functional neuroimaging evidence characterizing AD as a neural disconnection syndrome [3,4,5,6,7,8]. This connectivity impairment suggests the existence of abnormal interactions within and between neuronal systems in AD [5]. It could potentially lead to an early diagnosis marker of AD

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