title: Resting-state connectivity predicts levodopa-induced dyskinesias in Parkinson's disease.
abstract: BACKGROUND
  Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood.
  
  
  OBJECTIVE
  This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico-striatal connectivity.
  
  
  METHODS
  Twelve PD patients with peak-of-dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication. All patients received a single dose of fast-acting soluble levodopa and then underwent resting-state functional magnetic resonance imaging before any dyskinesias emerged. Levodopa-induced modulation of cortico-striatal resting-state connectivity was assessed between the putamen and the following 3 cortical regions of interest: supplementary motor area, primary sensorimotor cortex, and right inferior frontal gyrus. These functional connectivity measures were entered into a linear support vector classifier to predict whether an individual patient would develop dyskinesias after levodopa intake. Linear regression analysis was applied to test which connectivity measures would predict dyskinesia severity.
  
  
  RESULTS
  Dopaminergic modulation of resting-state connectivity between the putamen and primary sensorimotor cortex in the most affected hemisphere predicted whether patients would develop dyskinesias with a specificity of 100% and a sensitivity of 91% (P < .0001). Modulation of resting-state connectivity between the supplementary motor area and putamen predicted interindividual differences in dyskinesia severity (R(2) = 0.627, P = .004). Resting-state connectivity between the right inferior frontal gyrus and putamen neither predicted dyskinesia status nor dyskinesia severity.
  
  
  CONCLUSIONS
  The results corroborate the notion that altered dopaminergic modulation of cortico-striatal connectivity plays a key role in the pathophysiology of dyskinesias in PD.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Medical Research Council Brain Network Dynamics Unit at the University of Oxford, Oxford, United Kingdom.|Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Herz
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
authors.forename: Brian N
authors.initials: BN
authors.lastname: Haagensen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Silas H
authors.initials: SH
authors.lastname: Nielsen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Cognitive Systems, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Kristoffer H
authors.initials: KH
authors.lastname: Madsen
authors.affiliation: Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
authors.forename: Annemette
authors.initials: A
authors.lastname: Løkkegaard
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects*; D063132:Connectome / Q000379:methods*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011379:Prognosis; D011699:Putamen / Q000187:drug effects / Q000503:physiopathology*; D066191:Sensorimotor Cortex / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Parkinson's disease; dyskinesias; fMRI; levodopa MRI