Abstract
OBJECTIVE: To identify the spatial-temporal pattern variation of whole-brain functional connectivity (FC) during reward processing in melancholic major depressive disorder (MDD) patients, and to determine the clinical correlates of connectomic differences. METHODS: 61 MDD patients and 32 healthy controls were enrolled into the study. During magnetoencephalography (MEG) scanning, all participants completed the facial emotion recognition task. The MDD patients were further divided into two groups: melancholic (n = 31) and non-melancholic (n = 30), based on the Mini International Neuropsychiatric Interview (M.I.N.I.) assessment. Melancholic symptoms were examined by using the 6-item melancholia subscale from the Hamilton Depression Rating Scale (HAM-D6). The whole-brain orthogonalized power envelope connections in the high-beta band (20-35 Hz) were constructed in each period after the happy emotional stimuli (0-200 ms, 100-300 ms, 200-400 ms, 300-500 ms, and 400-600 ms). Then, the network-based statistic (NBS) was used to determine the specific abnormal connection patterns in melancholic MDD patients. RESULTS: The NBS identified a sub-network difference at the mid-late period (300-500 ms) in response to happy faces among the three groups (corrected P = 0.035). Then, the post hoc and correlation analyses found five FCs were decreased in melancholic MDD patients and were related to HAM-D6 score, including FCs of left fusiform gyrus-right orbital inferior frontal gyrus (r = -0.52, P < 0.001), left fusiform gyrus-left amygdala (r = -0.26, P = 0.049), left posterior cingulate gyrus-right precuneus (r = -0.32, P = 0.025), left precuneus-right precuneus (r = -0.27, P = 0.049), and left precuneus-left inferior occipital gyrus (r = -0.32, P = 0.025). CONCLUSION: In response to happy faces, melancholic MDD patients demonstrated a disrupted functional connective pattern (20-35 Hz, 300-500 ms), which involved brain regions in visual information processing and the limbic system. The aberrant functional connective pattern in reward processing might be a biomarker of melancholic MDD.