Positron Emission Tomography Reveals Abnormal Topological Organization In Functional Brain Network In Diabetic Patients

Objective:Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus(DM).However,the DM-related changes in the topological properties in functional brain networks are almost unexplored so far.We therefore used fluoro-D-glucose positron emission tomography(FDG-PET)data to construct functional brain networks,followed by a graph theoretical analysis.Materials and Methods:This was a retrospective analysis and all subjects were selected from a data pool in the PET Center of the First Affiliated Hospital of Dalian Medical University.A total of 73 diabetic patients(54 males,19 females)with a mean age of 57 ± 10 years,and 91 normal individuals(66 males,25 females)with a mean age of 56 ± 8 years,were selected into this study.First,Image format conversion,spatial normalization,and smoothing were performed during data processing using the MATLAB platform-based Statistical Parameters Mapping 8(SPM 8)software.Second,we used the automated anatomic labeling(AAL)template to divide the brain into 90 left-to-right symmetrical regions of interest(ROIs)to construct the inter-regional correlation matrix for glucose metabolism.Finally,we used graph theoretical approaches to investigate the differences of the brain functional network between DM patients and normal individuals based on FDG-PET data.Results: 1.Small-world topology of the functional networksThe brain functional networks of both the DM group and the NC group had the characteristics of "small-world" networks(? >1).For example,at all of the density thresholds,both networks had a large normalized cluster coefficient(? >>1)and a normalized shortest path length close to 1(? ~ 1).2.Altered small-world parameters in DM patients This study showed that the normalized clustering coefficient ? was significantly smaller in the DM group than in the NC group(density thresholds: 10%-22%,34%,36%-40%),the normalized shortest path length ? was significantly longer in the DM group than in the NC group(density threshold: 10%),and the small-world index ? was significantly smaller in the DM group than in the NC group(density thresholds: 10%-22%,34%,36%-40%)(P < 0.05).3.The distribution of the hub regions The DM had 21 hub regions,and the NC had 19.The two groups shared 5 hub regions.4.Altered nodal centrality in DM patientsThe centrality was significantly reduced in 4 brain regions: the right rectus,the right cuneus,the left middle occipital gyrus,and the left postcentral gyrus,and it was significantly increased in 3 brain regions: the orbitofrontal region of the left middle frontal gyrus,the left olfactory region,and the right paracentral lobule in the DM patients.Conclusion: Our result indicated that although functional PET network in diabetic patients preserved small-world characteristics,the topological properties in functional brain networks were found to be significantly changed,which may provide insights into the pathophysiology underlying diabetes-associated cognitive decline.Meanwhile,our study provide the functional evidence for the abnormalities of brain networks in DM.