Brain Functional Connectomics in Early Parkinson’s Disease (P2.005)

OBJECTIVE: To explore the integrity of the functional brain connectome in patients at different stages of Parkinson’s disease (PD). BACKGROUND: The study of connectomics in PD may shade light on the pathophysiology of the disease. DESIGN/METHODS: Graph theoretical analysis was applied to resting state fMRI data from 212 PD patients (100 with Hoehn and Yahr score [HY]=1-1.5, 54 with HY=2-2.5, 44 with HY=3-3.5, 14 with HY=4-5) and 46 matched healthy controls (HC). Functional connectivity between 90 cortical and subcortical brain regions was estimated using bivariate correlation analysis and thresholded to construct a set of undirected graphs. Measures of global (mean degree, clustering coefficient, global efficiency and characteristic path length) and regional (nodal degree and betweeness centrality) network properties were obtained. Correlations between UPDRS III score and network metrics were tested. RESULTS: Functional brain networks in PD and HC showed the same hub organization, with differences only in the right cingulum, left postcentral gyrus and precuneus bilaterally (hubs only in patients), and right fusiform gyrus (hub only in HC). However, all global network metrics were altered in PD patients. At a regional level, PD patients showed nodal degree reduction and betweeness centrality increase compared with HC. Such local abnormalities were relatively focal in patients with HY=1-1.5, involving the globus pallidus, putamen, supplementary motor area, cingulum, and gyrus rectus bilaterally, spreading to the frontal, temporal, parietal and occipital cortical regions in the more advanced disease stages. In PD, network metrics showed significant correlations with UPDRS III. CONCLUSIONS: In PD, functional brain networks are characterized by an imbalanced structure, with a loss of efficiency in information exchange between both close and distant brain areas. Abnormal functional network connectivity occurs even at the earliest stages of the disease and is an important factor contributing to PD motor deficits. Study Supported by: Italian Ministry of Health (#GR-2009-1577482); Ministry of Science and Technology of the Republic of Serbia (#175095).