title: Levodopa modulates small-world architecture of functional brain networks in Parkinson's disease.
abstract: PD is associated with disrupted connectivity to a large number of distributed brain regions. How the disease alters the functional topological organization of the brain, however, remains poorly understood. Furthermore, how levodopa modulates network topology in PD is largely unknown. The objective of this study was to use resting-state functional MRI and graph theory to determine how small-world architecture is altered in PD and affected by levodopa administration.
  
  
  
  Twenty-one PD patients and 20 controls underwent functional MRI scanning. PD patients were scanned off medication and 1 hour after 200 mg levodopa. Imaging data were analyzed using 226 nodes comprising 10 intrinsic brain networks. Correlation matrices were generated for each subject and converted into cost-thresholded, binarized adjacency matrices. Cost-integrated whole-brain global and local efficiencies were compared across groups and tested for relationships with disease duration and severity.
  
  
  
  Data from 2 patients and 4 controls were excluded because of excess motion. Patients off medication showed no significant changes in global efficiency and overall local efficiency, but in a subnetwork analysis did show increased local efficiency in executive (P = 0.006) and salience (P = 0.018) networks. Levodopa significantly decreased local efficiency (P = 0.039) in patients except within the subcortical network, in which it significantly increased local efficiency (P = 0.007).
  
  
  
  Levodopa modulates global and local efficiency measures of small-world topology in PD, suggesting that degeneration of nigrostriatal neurons in PD may be associated with a large-scale network reorganization and that levodopa tends to normalize the disrupted network topology in PD. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.|Neurology Section, Denver VA Medical Center, Denver, Colorado, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Berman
authors.affiliation: Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Smucny
authors.affiliation: Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Korey P
authors.initials: KP
authors.lastname: Wylie
authors.affiliation: Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Shelton
authors.affiliation: Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kronberg
authors.affiliation: Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Leehey
authors.affiliation: Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.|Research Service, Denver VA Medical Center, Denver, Colorado, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Tregellas
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D063132:Connectome; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Parkinson disease; graph theory; levodopa; resting-state fMRI