Virendra R Mishra1, Karthik R Sreenivasan2, Zhengshi Yang2, Xiaowei Zhuang2, Dietmar Cordes2, Zoltan Mari2, Irene Litvan2, Hubert H Fernandez2, David Eidelberg2, Aaron Ritter2, Jeffrey L Cummings2, Ryan R Walsh1. 1. From Imaging Research (V.R.M., K.R.S., Z.Y., X.Z., D.C.), Lou Ruvo Center for Brain Health (Z.M., A.R., J.L.C.), Cleveland Clinic Foundation, Las Vegas, NV; Departments of Psychology and Neuroscience (D.C.), University of Colorado at Boulder; Department of Neurosciences (I.L.), University of California San Diego, La Jolla; Center for Neurological Restoration (H.H.F.), Cleveland Clinic, OH; Center for Neurosciences (D.E.), Feinstein Institute for Medical Research, Manhasset, NY; UNLV Department of Brain Health (J.L.C.), School of Integrated Health Sciences, Las Vegas, NV; and Muhammad Ali Parkinson Center (R.R.W.), Barrow Neurological Institute, Phoenix, AZ. mishrav@ccf.org ryan.walsh@barrowneuro.org. 2. From Imaging Research (V.R.M., K.R.S., Z.Y., X.Z., D.C.), Lou Ruvo Center for Brain Health (Z.M., A.R., J.L.C.), Cleveland Clinic Foundation, Las Vegas, NV; Departments of Psychology and Neuroscience (D.C.), University of Colorado at Boulder; Department of Neurosciences (I.L.), University of California San Diego, La Jolla; Center for Neurological Restoration (H.H.F.), Cleveland Clinic, OH; Center for Neurosciences (D.E.), Feinstein Institute for Medical Research, Manhasset, NY; UNLV Department of Brain Health (J.L.C.), School of Integrated Health Sciences, Las Vegas, NV; and Muhammad Ali Parkinson Center (R.R.W.), Barrow Neurological Institute, Phoenix, AZ.
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.
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.
Authors: Werner Poewe; Klaus Seppi; Caroline M Tanner; Glenda M Halliday; Patrik Brundin; Jens Volkmann; Anette-Eleonore Schrag; Anthony E Lang Journal: Nat Rev Dis Primers Date: 2017-03-23 Impact factor: 52.329
Authors: Hu Cheng; Yang Wang; Jinhua Sheng; Olaf Sporns; William G Kronenberger; Vincent P Mathews; Tom A Hummer; Andrew J Saykin Journal: J Neurosci Methods Date: 2011-09-29 Impact factor: 2.390
Authors: J C Dalrymple-Alford; M R MacAskill; C T Nakas; L Livingston; C Graham; G P Crucian; T R Melzer; J Kirwan; R Keenan; S Wells; R J Porter; R Watts; T J Anderson Journal: Neurology Date: 2010-11-09 Impact factor: 9.910
Authors: Ming-Ching Wen; Hannah S E Heng; Jung-Lung Hsu; Zheyu Xu; Gerald M Liew; Wing Lok Au; Ling Ling Chan; Louis C S Tan; Eng King Tan Journal: Parkinsonism Relat Disord Date: 2017-09-21 Impact factor: 4.891
Authors: Anderson M Winkler; Gerard R Ridgway; Matthew A Webster; Stephen M Smith; Thomas E Nichols Journal: Neuroimage Date: 2014-02-11 Impact factor: 6.556
Authors: Jin Ho Jung; Yae Ji Kim; Seok Jong Chung; Han Soo Yoo; Yang Hyun Lee; Kyoungwon Baik; Seong Ho Jeong; Young Gun Lee; Hye Sun Lee; Byoung Seok Ye; Young H Sohn; Yong Jeong; Phil Hyu Lee Journal: J Neurol Date: 2021-11-11 Impact factor: 6.682
Authors: Maurizio Bergamino; Elizabeth G Keeling; Virendra R Mishra; Ashley M Stokes; Ryan R Walsh Journal: Front Neurol Date: 2020-05-14 Impact factor: 4.003
Authors: Xueling Suo; Du Lei; Nannan Li; Wenbin Li; Graham J Kemp; John A Sweeney; Rong Peng; Qiyong Gong Journal: Brain Struct Funct Date: 2021-04-07 Impact factor: 3.270
Authors: Dietmar Cordes; Muhammad F Kaleem; Zhengshi Yang; Xiaowei Zhuang; Tim Curran; Karthik R Sreenivasan; Virendra R Mishra; Rajesh Nandy; Ryan R Walsh Journal: Front Neurosci Date: 2021-05-21 Impact factor: 5.152
Authors: Thomas Hentrich; Zinah Wassouf; Christine Ehrhardt; Eva Haas; James D Mills; Eleonora Aronica; Tiago Fleming Outeiro; Jeannette Hübener-Schmid; Olaf Riess; Nicolas Casadei; Julia M Schulze-Hentrich Journal: Aging (Albany NY) Date: 2020-10-05 Impact factor: 5.682