VOXEL-BASED GRAPH THEORETICAL ANALYSIS OF FUNCTIONAL BRAIN NETWORKS IN PATIENTS WITH BEHAVIORAL VARIANT FRONTOTEMPORAL DEMENTIA

Abstract

Behavioral variant of frontotemporal dementia (bvFTD) is one of the main reasons of early dementia. The bvFTD patients usually will not accept treatment until their abnormal behaviors are very obvious, missing the opportunity of early behavior management and intervention. Hence, it would be of great scientific and social significance to find potential imaging markers for the early diagnosis of bvFTD. Graph theoretical analysis of human connectome may provide us this elusive biomarker because of several attributes of this approaches—low cost, safety, repeatability, and conceptual validity. We aimed to investigate the abnormality of the global network topology in patients with bvFTD. We selected participants (prospectively registered between June 2007–January 2017 in Peking University Institute of Mental Health) who had a baseline diagnosis of bvFTD and had completed a 3D T1 MRI examination (n=45). According to established criteria (Rascovsky et al., Brain 2011), 40 patients was diagnosed as probable bvFTD due to the neuroimaging evidence of frontal lobe atrophy (MRI visual rating scales and/or FDG-PET). A preliminary analysis of the R-fMRI data from 17 bvFTD patients and 23 matched normal controls was undertaken (The complete analysis will be conducted in February 2017). Firstly, we constructed the voxel-based whole-brain functional network of all subjects. Then, we analyzed the global topological properties, small-world parameters and nodal properties of the resultant network by utilizing the graph theoretical methods. Compared to controls, the clustering coefficient and modularity coefficient decreased in bvFTD, and the functional brain network organization deviates towards a random network. The bvFTD also showed altered degree in some nodes, which mainly located in the salience network, default-mode network and dorsal attention network. Global topological properties and small-world parameters are altered in bvFTD, indicating the inefficiency of local communication. Brain regions with altered nodal degree are located in networks that are closely associated with behavioral changes and cognitive deficits in bvFTD. These findings provide new insights into pathophysiological mechanisms of bvFTD and graph theoretical analysis maybe a promising markers to detect functional changes in the early phase of bvFTD.