Investigation on the Alteration of Brain Functional Network and Its Role in the Identification of Mild Cognitive Impairment

Lulu Zhang; Huangjing Ni; Zhinan Yu; Jun Wang; Jiaolong Qin; Fengzhen Hou; Albert Yang; Alzheimer’s Disease Neuroimaging Initiative (ADNI)

doi:10.3389/fnins.2020.558434

Investigation on the Alteration of Brain Functional Network and Its Role in the Identification of Mild Cognitive Impairment

Front Neurosci. 2020 Sep 30:14:558434. doi: 10.3389/fnins.2020.558434. eCollection 2020.

Authors

Lulu Zhang¹, Huangjing Ni², Zhinan Yu¹, Jun Wang², Jiaolong Qin³, Fengzhen Hou¹, Albert Yang⁴; Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Affiliations

¹ Key Laboratory of Biomedical Functional Materials, School of Science, China Pharmaceutical University, Nanjing, China.
² Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing, China.
³ Key Laboratory of Intelligent Perception and Systems for High-Dimensional Information of Ministry of Education, School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing, China.
⁴ Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, United States.

Abstract

Mild cognitive impairment (MCI) is generally regarded as a prodromal stage of Alzheimer's disease (AD). In coping with the challenges caused by AD, we analyzed resting-state functional magnetic resonance imaging data of 82 MCI subjects and 93 normal controls (NCs). The alteration of brain functional network in MCI was investigated on three scales, including global metrics, nodal characteristics, and modular properties. The results supported the existence of small worldness, hubs, and community structure in the brain functional networks of both groups. Compared with NCs, the network altered in MCI over all the three scales. In scale I, we found significantly decreased characteristic path length and increased global efficiency in MCI. Moreover, altered global network metrics were associated with cognitive level evaluated by neuropsychological assessments. In scale II, the nodal betweenness centrality of some global hubs, such as the right Crus II of cerebellar hemisphere (CERCRU2.R) and fusiform gyrus (FFG.R), changed significantly and associated with the severity and cognitive impairment in MCI. In scale III, although anatomically adjacent regions tended to be clustered into the same module regardless of group, discrepancies existed in the composition of modules in both groups, with a prominent separation of the cerebellum and a less localized organization of community structure in MCI compared with NC. Taking advantages of random forest approach, we achieved an accuracy of 91.4% to discriminate MCI patients from NCs by integrating cognitive assessments and network analysis. The importance of the used features fed into the classifier further validated the nodal characteristics of CERCRU2.R and FFG.R could be potential biomarkers in the identification of MCI. In conclusion, the present study demonstrated that the brain functional connectome data altered at the stage of MCI and could assist the automatic diagnosis of MCI patients.

Keywords: Alzheimer’s disease; graph theory; machine learning; mild cognitive impairment; modular structure; resting-state functional MRI.