title: Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.
abstract: Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional "disconnection" in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.
authors.affiliation: Division of Movement Disorders, Department of Neurology, Yale School of Medicine, New Haven, CT, USA; Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sule
authors.initials: S
authors.lastname: Tinaz
authors.affiliation: Office of the Clinical Director, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lauro
authors.affiliation: Office of the Clinical Director, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Parkinson's Disease and Movement Disorders Program, Department of Neurology, George Washington University, Washington, DC, USA.
authors.forename: Pritha
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Office of the Clinical Director, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Codrin
authors.initials: C
authors.lastname: Lungu
authors.affiliation: Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Silvina G
authors.initials: SG
authors.lastname: Horovitz
mesh_terms: D000328:Adult; D000368:Aged; D063132:Connectome / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology
keywords: Diffusion tensor imaging; Dopamine; Graph theory; Modularity; Neural network; Resting-state fMRI