Konrad Szewczyk-Krolikowski1, Ricarda A L Menke1, Michal Rolinski1, Eugene Duff1, Gholamreza Salimi-Khorshidi1, Nicola Filippini1, Giovanna Zamboni1, Michele T M Hu1, Clare E Mackay2. 1. 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. 2. 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.
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. CLASSIFICATION OF EVIDENCE: 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.
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. CLASSIFICATION OF EVIDENCE: 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.
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