title: Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson's Disease.
abstract: The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson's disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD.
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Koshimori
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Sang-Soo
authors.initials: SS
authors.lastname: Cho
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Marion
authors.initials: M
authors.lastname: Criaud
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Leigh
authors.initials: L
authors.lastname: Christopher
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Ghadery
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Coakeley
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto ON, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Harris
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto ON, Canada.
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
authors.affiliation: Division of Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto ON, Canada.
authors.forename: Clement
authors.initials: C
authors.lastname: Hamani
authors.affiliation: Morton and Gloria Shulman Movement Disorder Unit & E. J. Safra Parkinson Disease Program, Neurology Division, Department of Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Toronto ON, Canada.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto ON, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, TorontoON, Canada; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Research Institute, University Health Network, University of Toronto, TorontoON, Canada; Morton and Gloria Shulman Movement Disorder Unit & E. J. Safra Parkinson Disease Program, Neurology Division, Department of Medicine, Toronto Western Hospital, University Health Network, University of Toronto, TorontoON, Canada.
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Strafella
keywords: Parkinson’s disease; bradykinesia; brain network; cognitive impairment; resting-state functional MRI (rsfMRI)