Disrupted Causal Connectivity Anchored in the Posterior Cingulate Cortex in Amnestic Mild Cognitive Impairment.

Hong Yang,Feng Chen,Chengwei Wang,Zhan Feng,Jue Wang,Yumei Zhang,Shunliang Xu,Deqiang Li,Yushu Shi,Liming Xia,Haiyan Xie

doi:10.3389/fneur.2017.00010

Abstract

Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal cognitive aging and Alzheimer’s disease. Previous studies have found that neuronal activity and functional connectivity impaired in many functional networks, especially in the default mode network (DMN), which is related to significantly impaired cognitive and memory functions in aMCI patients. However, few studies have focused on the effective connectivity of the DMN and its subsystems in aMCI patients. The posterior cingulate cortex (PCC) is considered a crucial region in connectivity of the DMN and its key subsystem. In this study, using the coefficient Granger causality analysis approach and using the PCC as the region of interest, we explored changes in the DMN and its subsystems in effective connectivity with other brain regions as well as in correlations among them in 16 aMCI patients and 15 age-matched cognitively normal elderly. Results showed decreased effective connectivity from PCC to whole brain in the left prefrontal cortex, the left medial temporal lobe (MTL), the left fusiform gyrus (FG), and the left cerebellar hemisphere, meanwhile, right temporal lobe showed increased effective connectivity from PCC to the whole brain in aMCI patients compared with normal control. In addition, compared with the normal controls, increased effective connectivity of the whole brain to the PCC in aMCI patients was found in the right thalamus, left medial temporal lobe, left FG, and left cerebellar hemisphere. Compared with the normal controls, no reduced effective connectivity was found in any brain regions from the whole brain to the PCC in aMCI patients. The reduced effective connectivity of the PCC to left MTL showed negative correlation trend with neuropsychological tests (Auditory Verbal Learning Test-immediate recall and clock drawing test) in aMCI patients. Our study shows that aMCI patients have abnormalities in effective connectivity within the PCC-centered DMN network and its posterior subsystems as well as in the cerebellar hemisphere and thalamus. Abnormal integration of networks may be related to cognitive and memory impairment and compensation mechanisms in aMCI patients.

Highlights

Alzheimer’s disease (AD) is a common neurodegenerative disease that presents mainly with memory impairment and decline in cognitive function
All Amnestic mild cognitive impairment (aMCI) patients fulfilled the criteria by Petersen et al [1] as follows: [1] main complaint of memory impairment for more than 6 months and confirmed by the subject and an informant, [2] impaired memory function for age and education documented by an Auditory Verbal Learning Test (AVLT)-delayed recall score that is less than or equal to 1.5 SD of age-adjusted and education-adjusted norms, [3] preserved general cognitive function evaluated by a mini–mental state examination (MMSE) score of 24 or higher, [4] intact activities of daily living (ADL), through a history from the subject and informant, and [5] not demented
Compared with the normal group, the aMCI patients demonstrated increased effective connectivity from the whole brain to posterior cingulate cortex (PCC) in the right thalamus, left medial temporal lobe, left fusiform gyrus (FG), and left cerebellar hemisphere, and no reduced effective connectivity was found in any brain regions (Table 2 and Figure 3)

Summary

Introduction

Alzheimer’s disease (AD) is a common neurodegenerative disease that presents mainly with memory impairment and decline in cognitive function. Zhang et al used a regional homogeneity (ReHo) method to study AD, MCI, and normal control groups and found that in AD and MCI patients, results indicated reduced ReHo values in the medial prefrontal cortex (mPFC), the bilateral posterior cingulate cortex (PCC)/cuneus, and the left inferior parietal lobe (IPL) as well as decreased memory and cognitive ability. The lower ReHo values in AD and MCI patients suggested that cognitive and memory impairment were correlated with decreased spontaneous brain activity. The MCI group showed increased ReHo values in the left IPL when compared with the control group, suggesting compensation for the impaired cognitive regions [2]

Objectives

Methods

Results

Discussion

Conclusion