title: Functional connectivity in the basal ganglia network differentiates PD patients from controls.
abstract: OBJECTIVE
  To examine functional connectivity within the basal ganglia network (BGN) in a group of cognitively normal patients with early Parkinson disease (PD) on and off medication compared to age- and sex-matched healthy controls (HC), and to validate the findings in a separate cohort of participants with PD.
  
  
  METHODS
  Participants were scanned with resting-state fMRI (RS-fMRI) at 3T field strength. Resting-state networks were isolated using independent component analysis. A BGN template was derived from 80 elderly HC participants. BGN maps were compared between 19 patients with PD on and off medication in the discovery group and 19 age- and sex-matched controls to identify a threshold for optimal group separation. The threshold was applied to 13 patients with PD (including 5 drug-naive) in the validation group to establish reproducibility of findings.
  
  
  RESULTS
  Participants with PD showed reduced functional connectivity with the BGN in a wide range of areas. Administration of medication significantly improved connectivity. Average BGN connectivity differentiated participants with PD from controls with 100% sensitivity and 89.5% specificity. The connectivity threshold was tested on the validation cohort and achieved 85% accuracy.
  
  
  CONCLUSIONS
  We demonstrate that resting functional connectivity, measured with MRI using an observer-independent method, is reproducibly reduced in the BGN in cognitively intact patients with PD, and increases upon administration of dopaminergic medication. Our results hold promise for RS-fMRI connectivity as a biomarker in early PD.
  
  
  METHODS
  This study provides Class III evidence that average connectivity in the BGN as measured by RS-fMRI distinguishes patients with PD from age- and sex-matched controls.
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Konrad
authors.initials: K
authors.lastname: Szewczyk-Krolikowski
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Ricarda A L
authors.initials: RA
authors.lastname: Menke
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Michal
authors.initials: M
authors.lastname: Rolinski
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Eugene
authors.initials: E
authors.lastname: Duff
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Salimi-Khorshidi
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zamboni
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK.
authors.forename: Michele T M
authors.initials: MT
authors.lastname: Hu
authors.affiliation: From the Nuffield Department of Clinical Neurosciences (K.S.-K., M.R., M.H.), Oxford Parkinson's Disease Centre (OPDC) (K.S.-K., R.A.L.M., M.R., M.T.M.H., C.E.M.), Department of Psychiatry (C.E.M.), and FMRIB Centre (R.A.L.M., E.D., G.S.-K., N.F., G.Z., C.E.M.), University of Oxford, UK. clare.mackay@psych.ox.ac.uk.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Mackay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000503:physiopathology*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D059907:Functional Neuroimaging / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D010300:Parkinson Disease / Q000175:diagnosis / Q000503:physiopathology*