Objectives: To investigate whether functional connectivity (FC) differs in Parkinson’s disease (PD) patients with different levodopa responsiveness.

Materials and Methods: Forty-eight idiopathic PD (iPD) patients were enrolled and scanned using a STAGE protocol plus resting-state functional MRI (rs-fMRI) at 3.0 T. Anatomical images using high-resolution susceptibility-weighted imaging with FA of 27 degree were normalized and segmented via FreeSurfer. Rs-fMRI was processed under slice timing, motion correction, normalization, smoothing and denoising with CONN. ROI-to-ROI and seed-based FC analyses were subsequently made. Bilateral deep grey matters (DGM) including caudate nucleus (CN), globus pallidus (GP), putamen (PUT), substantia nigra (SN), red nucleus (RN), and dentate nucleus （DN）were defined as target seeds. AAL3 atlas (excluding target seeds) and DGM atlas (generated via in-house software) were used. The levodopa responsiveness was assessed by the improved rate of UPDRS-III after levodopa challenge test. The good and moderate responsiveness was defined by the improved rate of at least and no more than 38% (median split), respectively.

Results：Twenty-seven iPD patients were good responders. Significant increase of FC between [left frontal operculum cortex (FO l), left inferior frontal gyrus pars opercularis left (IFG oper l), left inferior frontal gyrus pars triangularis left (IFG tri l)] and [right frontal orbital cortex (FOrb r), left frontal orbital cortex (FOrb l)] was noticed in good responders (ROI-to-ROI, cluster-based inference, pFDR<0.05). As for seed-based analysis, increased FC was found between right caudate and [Temporal Pole Left (TP l) and Temporal Fusiform Cortex, anterior division Left (aTFusC l)], right pallidum and Lateral Occipital Cortex, superior division Right (sLOC r), right putamen and [Middle Temporal Gyrus, temporooccipital part Right (toMTG r) and Middle Temporal Gyrus, posterior division Right (pMTG r)], left red nucleus and [Left and Right Lateral Occipital Cortex, inferior division (iLOC l)], right red nucleus and [Cerebelum Crus1 Right and Cerebelum 6 Right, Postcentral Gyrus Left (PostCG l) and Unknown (near cingulate gyrus)], respectively in good responders (pFDR<0.05).

Conclusion: In addition to the increased FC of cortical motor centers, striatum and red nucleus might have reaction with temporooccipital cortex and cerebellum in PD with different levodopa responsiveness.