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

Neurology. 2020 Feb 25;94(8):e774-e784. doi: 10.1212/WNL.0000000000008867. Epub 2019 Dec 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*