Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

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Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal cognitive aging and Alzheimer’s disease. Previous studies have found that neuronal activity and functional connectivity impaired in many functional networks, especially in the default mode network (DMN), which is related to significantly impaired cognitive and memory functions in aMCI patients. However, few studies have focused on the effective connectivity of the DMN and its subsystems in aMCI patients. The posterior cingulate cortex (PCC) is considered a crucial region in connectivity of the DMN and its key subsystem. In this study, using the coefficient Granger causality analysis approach and using the PCC as the region of interest, we explored changes in the DMN and its subsystems in effective connectivity with other brain regions as well as in correlations among them in 16 aMCI patients and 15 age-matched cognitively normal elderly. Results showed decreased effective connectivity from PCC to whole brain in the left prefrontal cortex, the left medial temporal lobe (MTL), the left fusiform gyrus (FG), and the left cerebellar hemisphere, meanwhile, right temporal lobe showed increased effective connectivity from PCC to the whole brain in aMCI patients compared with normal control. In addition, compared with the normal controls, increased effective connectivity of the whole brain to the PCC in aMCI patients was found in the right thalamus, left medial temporal lobe, left FG, and left cerebellar hemisphere. Compared with the normal controls, no reduced effective connectivity was found in any brain regions from the whole brain to the PCC in aMCI patients. The reduced effective connectivity of the PCC to left MTL showed negative correlation trend with neuropsychological tests (Auditory Verbal Learning Test-immediate recall and clock drawing test) in aMCI patients. Our study shows that aMCI patients have abnormalities in effective connectivity within the PCC-centered DMN network and its posterior subsystems as well as in the cerebellar hemisphere and thalamus. Abnormal integration of networks may be related to cognitive and memory impairment and compensation mechanisms in aMCI patients.

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