From Local To Remote Functional Connectivity Changes In Drug-naive Patients With Parkinson’s Disease

Background:Parkinson’s disease(PD)is increasingly conceptualized as a progressive neurological disorder of brain networks.Resting-state functional magnetic resonance imaging studies have reported abnormalities of the local and remote functional connectivity(FC)in patients with PD.However,few studies have investigated aberrant remote FC associated with local FC in PD.Methods:Resting-state regional homogeneity(Re Ho)was used to analyze differences of local FC in early drug-naive patients with PD and healthy matched controls.The aberrant Re Ho areas in PD were defined as regions of interest(ROIs)for further remote FC analysis.Correlation analyses between local and remote FC and clinical variables were conducted.Results:No significant differences were observed regarding age,gender,educational level,handedness,cognition or depression evaluations in patients with PD and healthy controls(all p > 0.05).Compared to healthy controls,PD patients had decreased Re Ho in the right supplementary motor area(SMA)extending to the left SMA and left putamen.Remote FC based on the seed-based correlation approach showed enhanced connectivity between the SMA and left putamen and between the left putamen and the right precentral gyrus,SMA,and right putamen.Moreover,motor impairment was negatively correlated with above-mentioned enhanced FC.No significant correlations were observed between the Re Ho and motor impairment,disease duration,disease severity,cognition or depression evaluation in the PD group(all p > 0.05).Neither were there correlations between the remote FC and disease duration,disease severity,cognition,or depression evaluation in the PD group(all p >0.05).Conclusions:The current study demonstrated decreased local FC and enhanced remote FC in the cortico-striatal-thalamo-cortical circuit(CSTC).Aberrant local–remote FC may be a neurodegenerative feature underlying PD.Compensation of the remote FC in the CSTC may be an imaging biomarker for monitoring progression of motor impairment in PD.