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Open Access Publications from the University of California

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

  • Author(s): 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
  • et al.

OBJECTIVE: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). METHODS: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. RESULTS: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. CONCLUSION: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.

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