Patients with Parkinson's disease (PD) have difficulty in performing self-initiated movements. The neural mechanism of this deficiency remains unclear. In the current study, we used functional MRI (fMRI) and psychophysiological interaction (PPI) methods to investigate the changes in effective connectivity of the brain networks during performance of self-initiated movement in PD patients. Effective connectivity is defined as the influence one neuronal system exerts over another. fMRIs were acquired in 18 PD patients and in 18 age- and sex-matched healthy controls, when performing a self-initiated right hand tapping task. We chose the left primary motor cortex (M1), rostral supplementary motor area (pre-SMA), left premotor cortex (PMC), left putamen, and right cerebellum as index areas for PPI analysis. During the performance of self-initiated movement, connectivity between the putamen and M1, PMC, SMA, and cerebellum was decreased in PD patients compared to controls. In contrast, connections between the M1, pre-SMA, PMC, parietal cortex, and cerebellum were increased in PD patients compared to controls. In addition, the M1, pre-SMA, PMC, and cerebellum also had less connectivity with the dorsal lateral prefrontal cortex in PD. In PD patients, the effective connectivity between the putamen and M1, PMC, SMA, and cerebellum negatively correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores; whereas the connectivity between the M1, pre-SMA, PMC, and cerebellum positively correlated with the UPDRS motor scores. Our findings demonstrate that the pattern of interactions of brain networks is disrupted in PD during performance of self-initiated movements. The striatum-cortical and striatum-cerebellar connections are weakened. In contrast, the connections between cortico-cerebellar motor regions are strengthened and may compensate for basal ganglia dysfunction. These altered interregional connections are more deviant when the disorder is more severe, and, therefore, our results give further insight into the explanation for the difficulty in performing self-initiated movements in PD. (c) 2010 Elsevier Inc. All rights reserved.