Abnormal functional connectivity density in Parkinson's disease

•Voxel-wise contrasts of FCD were performed between PD patients and controls.•PD showed decreased FCD mainly in the ventral stream and frontal regions.•PD showed increased FCD in bilateral precuneus and PCC. The pathology of Parkinson's disease (PD) is not confined to the nigrostriatal pathway, but also involves widespread cerebral cortical areas. Using seed-based resting state functional connectivity, many previous studies have demonstrated that PD patients have abnormal functional integration. However, this technique strongly relies on a priori selection of the seed regions and may miss important unpredictable findings. Using an ultrafast voxel-wise functional connectivity density approach, this study performed a whole brain functional connectivity analysis to investigate the abnormal resting-state functional activities in PD patients. Compared with healthy controls, PD patients exhibited decreased short-range functional connectivity densities in regions that were mainly located in the ventral visual pathway and decreased long-range functional connectivity densities in the right middle and superior frontal gyrus, which have been speculated to be associated with visual hallucinations and cognitive dysfunction, respectively. PD patients also exhibited increased short- and long-range functional connectivity densities in the bilateral precuneus and posterior cingulate cortex, which may represent a compensatory process for maintaining normal brain function. The observed functional connectivity density alterations might be related to the disturbed structural connectivity of PD patients, leading to abnormal functional integration. Our results suggest that functional connectivity density mapping may provide a useful means to assess PD-related neurodegeneration and to study the pathophysiology of PD.