Altered Brain Activity in Depression of Parkinson’s Disease: A Meta-Analysis and Validation Study

BACKGROUND: The pathophysiology of depression in Parkinson’s disease (PD) is not fully understood. Studies based upon functional MRI (fMRI) showed the alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain regions pertaining to depression in PD. However, large variance was observed across previous studies. Therefore, we conducted a meta-analysis to quantitatively evaluate the results in previous publications and completed an independent regions-of-interests (ROIs)-based analysis using our own data to validate the results of the meta-analysis. METHODS: We searched PubMed, Embase, and Web of Science to identify fMRI studies in PD patients with depression. Using signed differential mapping (SDM) method, we performed a voxel-based meta-analysis. Then, a validation study by using multiscale entropy (MSE) in 28 PD patients with depression and 25 PD patients without depression was conducted. The fMRI scan was completed in anti-depression-medication-off state. The ROIs of the MSE analysis were the regions identified by the meta-analysis. RESULTS: A total of 126 PD patients with depression and 153 PD patients without depression were included in meta-analysis. It was observed that the resting-state activities within the posterior cingulate gyrus, supplementary motor area (SMA), and cerebellum were altered in depressed patients. Then, in the validation study, these regions were used as ROIs. PD patients with depression had significantly lower MSE of the BOLD fluctuations in these regions (posterior cingulate gyrus: F = 0.856, p = 0.049; SMA: F = 0.914, p = 0.039; cerebellum: F = 0.227, p = 0.043). CONCLUSION: Our study revealed that the altered BOLD activity in cingulate, SMA, and cerebellum of the brain were pertaining to depression in PD.