Unique white matter structural connectivity in early-stage drug-naive Parkinson disease

• Published in: Neurology Vol. 94; no. 8; p. e774
• Main Authors: Mishra, Virendra R, Sreenivasan, Karthik R, Yang, Zhengshi, Zhuang, Xiaowei, Cordes, Dietmar, Mari, Zoltan, Litvan, Irene, Fernandez, Hubert H, Eidelberg, David, Ritter, Aaron, Cummings, Jeffrey L, Walsh, Ryan R
• Format: Journal Article
• Language: English
• Published: United States 25.02.2020
• Subjects: Aged; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Nerve Net - diagnostic imaging; Nerve Net - pathology; Parkinson Disease - diagnostic imaging; Parkinson Disease - pathology; White Matter - diagnostic imaging; White Matter - pathology
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000008867

To investigate the topographic arrangement and strength of whole-brain white matter (WM) structural connectivity in patients with early-stage drug-naive Parkinson disease (PD). We employed a model-free data-driven approach for computing whole-brain WM topologic arrangement and connectivity strength between brain regions by utilizing diffusion MRI of 70 participants with early-stage drug-naive PD and 41 healthy controls. Subsequently, we generated a novel group-specific WM anatomical network by minimizing variance in anatomical connectivity of each group. Global WM connectivity strength and network measures were computed on this group-specific WM anatomical network and were compared between the groups. We tested correlations of these network measures with clinical measures in PD to assess their pathophysiologic relevance. PD-relevant cortical and subcortical regions were identified in the novel PD-specific WM anatomical network. Impaired modular organization accompanied by a correlation of network measures with multiple clinical variables in early PD were revealed. Furthermore, disease duration was negatively correlated with global connectivity strength of the PD-specific WM anatomical network. By minimizing variance in anatomical connectivity, this study found the presence of a novel WM structural connectome in early PD that correlated with clinical symptoms, despite the lack of a priori analytic assumptions. This included the novel finding of increased structural connectivity between known PD-relevant brain regions. The current study provides a framework for further investigation of WM structural changes underlying the clinical and pathologic heterogeneity of PD.