Functional connectivity markers of depression in advanced Parkinson's disease

Background: Depression is a common comorbid condition in Parkinson's disease and a major contributor to poor quality of life. Despite this, depression in PD is under-diagnosed due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired old patients. Objectives: This study is to explore functional connectivity markers of depression in PD patients using resting-state fMRI and help diagnose whether patients have depression or not. Methods: We reviewed 156 advanced PD patients (duration > 5 years; 59 depressed ones) and 45 healthy control subjects who underwent a resting-state fMRI scanning. Functional connectivity analysis was employed to characterize intrinsic connectivity networks using group independent component analysis and extract connectivity features. Features were put into an all-relevant feature selection procedure within cross-validation loops, to identify features with significant discriminative power for classification. Random forest classifiers were built for depression diagnosis, on the basis of identified features. Results: 42 intrinsic connectivity networks were identified and arranged into subcortical, auditory, somatomotor, visual, cognitive control, default-mode and cerebellar networks. Six features were significantly relevant to classification. They were connectivity within posterior cingulate cortex, within insula, between posterior cingulate cortex and insula/hippocampus+amygdala, between insula and precuneus, and between superior parietal lobule and medial prefrontal cortex. The mean accuracy achieved with classifiers to discriminate depressed patients from the non-depressed was 82.4%. Conclusions: Our findings provide preliminary evidence that resting-state functional connectivity can characterize depressed PD patients and help distinguish them from non-depressed ones. Keywords: Parkinson's disease, Depression, Resting-state fMRI, Intrinsic connectivity network, Functional connectivity