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Original Research ARTICLE

Front. Hum. Neurosci., 09 August 2013 | http://dx.doi.org/10.3389/fnhum.2013.00456

Modular reorganization of brain resting state networks and its independent validation in Alzheimer's disease patients

Guangyu Chen1, Hong-Ying Zhang2,3, Chunming Xie1,4, Gang Chen1, Zhi-Jun Zhang4, Gao-Jun Teng2* and Shi-Jiang Li1,5*
  • 1Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA
  • 2Department of Radiology, Jiangsu Key Laboratory of Molecule Imaging and Functional Imaging, Medical School of Southeast University, Nanjing, PR China
  • 3Department of Radiology, Subei People's Hospital of Jiangsu Province, Yangzhou University, Yangzhou, PR China
  • 4Department of Neuropsychiatry, Affiliated Zhong Da Hospital of Southeast University, Nanjing, PR China
  • 5Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

Previous studies have demonstrated disruption in structural and functional connectivity occurring in the Alzheimer's Disease (AD). However, it is not known how these disruptions alter brain network reorganization. With the modular analysis method of graph theory, and datasets acquired by the resting-state functional connectivity MRI (R-fMRI) method, we investigated and compared the brain organization patterns between the AD group and the cognitively normal control (CN) group. Our main finding is that the largest homotopic module (defined as the insula module) in the CN group was broken down to the pieces in the AD group. Specifically, it was discovered that the eight pairs of the bilateral regions (the opercular part of inferior frontal gyrus, area triangularis, insula, putamen, globus pallidus, transverse temporal gyri, superior temporal gyrus, and superior temporal pole) of the insula module had lost symmetric functional connection properties, and the corresponding gray matter concentration (GMC) was significant lower in AD group. We further quantified the functional connectivity changes with an index (index A) and structural changes with the GMC index in the insula module to demonstrate their great potential as AD biomarkers. We further validated these results with six additional independent datasets (271 subjects in six groups). Our results demonstrated specific underlying structural and functional reorganization from young to old, and for diseased subjects. Further, it is suggested that by combining the structural GMC analysis and functional modular analysis in the insula module, a new biomarker can be developed at the single-subject level.

Keywords: Alzheimer's disease, MCI, validation, module analysis, resting-state functional connectivity, brain network, gray matter concentration, graph theory

Citation: Chen G, Zhang H-Y, Xie C, Chen G, Zhang Z-J, Teng G-J and Li S-J (2013) Modular reorganization of brain resting state networks and its independent validation in Alzheimer's disease patients. Front. Hum. Neurosci. 7:456. doi: 10.3389/fnhum.2013.00456

Received: 06 May 2013; Accepted: 22 July 2013;
Published online: 09 August 2013.

Edited by:

Yong He, Beijing Normal University, China

Reviewed by:

Christian Sorg, Klinikum rechts der Isar Technische Universität München, Germany
Jinhui Wang, Beijing Normal University, China

Copyright © 2013 Chen, Zhang, Xie, Chen, Zhang, Teng and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Gao-Jun Teng, Department of Radiology, Jiangsu Key Laboratory of Molecule Imaging and Functional Imaging, Medical School of Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, PR China e-mail: gjteng@vip.sina.com;
Shi-Jiang Li, Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA e-mail: sjli@mcw.edu