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Abstract
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.
Glossary
- AD=
- Alzheimer disease;
- DaT=
- dopamine uptake transporter;
- dMRI=
- diffusion MRI;
- FA=
- fractional anisotropy;
- FW=
- free-water;
- HC=
- healthy controls;
- Inf-Fron-Tri-Left=
- left frontal inferior triangularis;
- MDS-UPDRS-III=
- Movement Disorder Society–sponsored Unified Parkinson's Disease Rating Scale Part III;
- MNI=
- Montreal Neurological Institute;
- MoCA=
- Montreal Cognitive Assessment;
- NBS=
- network-based statistic;
- PALM=
- permutation analysis of linear models;
- PD=
- Parkinson disease;
- PPMI=
- Parkinson's Progression Markers Initiative;
- ROI=
- region of interest;
- SMA=
- supplementary motor area;
- WM=
- white matter
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received April 29, 2019.
- Accepted in final form August 28, 2019.
- © 2019 American Academy of Neurology
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