PMID- 29549664 OWN - NLM STAT- MEDLINE DCOM- 20190610 LR - 20190613 IS - 1931-7565 (Electronic) IS - 1931-7557 (Linking) VI - 13 IP - 1 DP - 2019 Feb TI - Altered effective connectivity anchored in the posterior cingulate cortex and the medial prefrontal cortex in cognitively intact elderly APOE epsilon4 carriers: a preliminary study. PG - 270-282 LID - 10.1007/s11682-018-9857-5 [doi] AB - The APOE epsilon4 allele is associated with impaired intrinsic functional connectivity in neural networks, especially in the default mode network (DMN). However, effective connectivity (EC) reflects the direct causal effects of one brain region to another, which has rarely been investigated. Recently, Granger causality analysis (GCA) proved suitable for the study of directionality in neuronal interactions. Using GCA, we examined the differences in the EC between the anterior medial prefrontal cortex/posterior cingulate cortex (aMPFC/PCC) and the whole brain in 17 epsilon4 carrying and 32 non-carrying cognitively intact elderly individuals. Furthermore, correlation analyses were performed between the abnormal EC and cognition/neuropathological indices. Compared with the non-carriers, the results showed that the epsilon4 carriers exhibited decreased EC from the PCC to the whole brain in the middle temporal gyrus (MTG), the anterior cingulate cortex (ACC), and the precuneus (PCu). Meanwhile, the epsilon4 carriers demonstrated increased EC from the whole brain to the aMPFC in the inferior parietal lobe (IPL) and the postcentral gyrus (PCG). The correlation analyses suggested that the EC from the IPL/PCG to the aMPFC was related to episodic memory in non-carriers, while the decreased EC from the PCC to the ACC was associated with increased levels of t-tau in the epsilon4 carriers. In epsilon4 carriers, a negative influence can be traced from the PCC to both the anterior and posterior DMN subsystems; meanwhile, the anterior DMN subsystem receives compensatory effects from the parietal cortex. Early increases in AD-related pathologies in the PCC may act as first factors during this pathological process. FAU - Luo, Xiao AU - Luo X AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Li, Kaicheng AU - Li K AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Jia, Y L AU - Jia YL AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Zeng, Qingze AU - Zeng Q AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Jiaerken, Yeerfan AU - Jiaerken Y AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Qiu, Tiantian AU - Qiu T AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Huang, Peiyu AU - Huang P AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Xu, Xiaojun AU - Xu X AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Shen, Zhujing AU - Shen Z AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Guan, Xiaojun AU - Guan X AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Zhou, Jiong AU - Zhou J AD - Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. FAU - Wang, Chao AU - Wang C AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Xu, J J AU - Xu JJ AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. FAU - Zhang, Minming AU - Zhang M AUID- ORCID: 0000-0003-0145-7558 AD - Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jie-Fang Road, Shang-Cheng District, Hangzhou, 310009, China. zhangminming@zju.edu.cn. CN - Alzheimer's Disease Neuroimaging Initiative (ADNI) LA - eng GR - NO.2016YFC1306600/National Key Research and Development Program of China/ GR - NO. 2017XZZX001-01/Fundamental Research Funds for the Central Universities/ GR - Grant NO. LZ14H180001/Zhejiang Provincial Natural Science Foundation of China/ GR - NO.2015KYB174/Projects of Medical and Health Technology Development Program in Zhejiang Province/ GR - NO.2018ZQ035/Young Talents Research Fund, Chinese Medicine Science and Technology Project of Zhejiang Province/ PT - Journal Article PL - United States TA - Brain Imaging Behav JT - Brain imaging and behavior JID - 101300405 RN - 0 (Apolipoprotein E4) SB - IM MH - Aged MH - Aging/*genetics/*physiology MH - Apolipoprotein E4/*genetics MH - Brain Mapping/methods MH - Cross-Sectional Studies MH - Female MH - Gyrus Cinguli/diagnostic imaging/*physiopathology MH - Heterozygote MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Neural Pathways/diagnostic imaging/physiopathology MH - Prefrontal Cortex/diagnostic imaging/*physiopathology MH - Preliminary Data MH - Rest OTO - NOTNLM OT - APOE OT - Cerebrospinal fluid OT - Effective connectivity OT - Granger causality analysis, Default mode network OT - Resting-state functional MRI EDAT- 2018/03/20 06:00 MHDA- 2019/06/14 06:00 CRDT- 2018/03/18 06:00 PHST- 2018/03/20 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2018/03/18 06:00 [entrez] AID - 10.1007/s11682-018-9857-5 [pii] AID - 10.1007/s11682-018-9857-5 [doi] PST - ppublish SO - Brain Imaging Behav. 2019 Feb;13(1):270-282. doi: 10.1007/s11682-018-9857-5.