PT  - JOURNAL ARTICLE
AU  - Mishra, Virendra R.
AU  - Sreenivasan, Karthik R.
AU  - Yang, Zhengshi
AU  - Zhuang, Xiaowei
AU  - Cordes, Dietmar
AU  - Mari, Zoltan
AU  - Litvan, Irene
AU  - Fernandez, Hubert H.
AU  - Eidelberg, David
AU  - Ritter, Aaron
AU  - Cummings, Jeffrey L.
AU  - Walsh, Ryan R.
TI  - Unique white matter structural connectivity in early-stage drug-naive Parkinson disease
AID  - 10.1212/WNL.0000000000008867
DP  - 2020 Feb 25
TA  - Neurology
PG  - e774--e784
VI  - 94
IP  - 8
4099  - http://n.neurology.org/content/94/8/e774.short
4100  - http://n.neurology.org/content/94/8/e774.full
SO  - Neurology2020 Feb 25; 94
AB  - 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.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