Brain connectivity for subtypes of parkinson’s disease using structural MRI

Abstract

Objective: Delineating Parkinson’s disease (PD) into distinct subtypes is a major challenge. Most studies use clinical symptoms to label PD subtypes while our work uses an imaging-based data-mining approach to subtype PD. Our study comprises of two major objectives - firstly, subtyping Parkinson’s patients based on grey matter information from structural magnetic resonance imaging scans of human brains; secondly, comparative structural brain connectivity analysis of PD subtypes derived from the former step. Approach: Source-based-morphometry decomposition was performed on 131 Parkinson’s patients and 78 healthy controls from PPMI dataset, to derive at components (regions) with significance in disease and high effect size. The loading coefficients of significant components were thresholded for arriving at subtypes. Further, regional grey matter maps of subtype-specific subjects were separately parcellated and employed for construction of subtype-specific association matrices using Pearson correlation. These association matrices were binarized using sparsity threshold and leveraged for structural brain connectivity analysis using network metrics. Main results: Two distinct Parkinson’s subtypes (namely A and B) were detected employing loadings of two component satisfying the selection criteria, and a third subtype (AB) was detected, common to these two components. Subtype A subjects were highly weighted in inferior, middle and superior frontal gyri while subtype B subjects in inferior, middle and superior temporal gyri. Network metrics analyses through permutation test revealed significant inter-subtype differences (p<0.05) in clustering coefficient, local efficiency, participation coefficient and betweenness centrality. Moreover, hubs were obtained using betweenness centrality and mean network degree. Significance: MRI-based data-driven subtypes show frontal and temporal lobe playing key role in PD. Graph theory-driven brain network analyses could untangle subtype-specific differences in structural brain connections showing differential network architecture. Replication of these initial results in other Parkinson’s datasets may be explored in future. Clinical Relevance- Investigating structural brain connections in Parkinson's disease may provide subtype-specific treatment.