Labeling subtypes in a Parkinson's Cohort using Multifeatures in MRI -- Integrating Grey and White Matter Information

Abstract: Thresholding of networks has long posed a challenge in brain connectivity analysis. Weighted networks are typically binarized using threshold measures to facilitate network analysis. Previous studies on MRI-based brain networks have predominantly utilized density or sparsity-based thresholding techniques, optimized within specific ranges derived from network metrics such as path length, clustering coefficient, and small-world index. Thus, determination of a single threshold value for facilitating comparative analysis of networks remains elusive. To address this, our study introduces Mutual K-Nearest Neighbor (MKNN)-based thresholding for brain network analysis. Here, nearest neighbor selection is based on the highest correlation between features of brain regions. Construction of brain networks was accomplished by computing Pearson correlations between grey matter volume and white matter volume for each pair of brain regions. Structural MRI data from 180 Parkinsons patients and 70 controls from the NIMHANS, India were analyzed. Subtypes within Parkinsons disease were identified based on grey and white matter volume atrophy using source-based morphometric decomposition. The loading coefficients were correlated with clinical features to discern clinical relationship with the deciphered subtypes. Our data-mining approach revealed: Subtype A (N = 51, intermediate type), Subtype B (N = 57, mild-severe type with mild motor symptoms), and Subtype AB (N = 36, most-severe type with predominance in motor impairment). Subtype-specific weighted matrices were binarized using MKNN-based thresholding for brain network analysis. Permutation tests on network metrics of resulting bipartite graphs demonstrated significant group differences in betweenness centrality and participation coefficient. The identified hubs were specific to each subtype, with some hubs conserved across different subtypes.