Characterizing gradients of functional connectome underpinning rumination and their alteration in depression

As a prominent psychopathological process of major depression disorder (MDD), rumination’s brain underpinnings remain unclear. Emerging studies have highlighted that brain areas are organized along several macroscale gradients, which could be a powerful framework to better understand how the functional connectome was organized to underlie rumination. In this study, two datasets (Rum-Beijing and Rum-MDD) were leveraged in the present study. Rum-Beijing consisted of 41 healthy controls (HC) who underwent 3 repetitive scans, while Rum-MDD consisted of 45 patients with major depressive disorder (MDD) and 46 HCs. We used a modified rumination state task (RST) to induce participants into a continuous, active rumination state and characterized the gradient profiles. RST also included a distraction state as the control condition. The explanation ratio of gradient and the regional differences of each gradient were also compared. Leveraging the Rum-MDD dataset, we further examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) regarding the gradient’s global and local metrics. Two gradients were identified: the primary-transmodal gradient and the visual-sensorimotor gradient. We found that the rumination state exhibited reduced gradient values in the default mode network (DMN) but elevated gradient values in the frontoparietal network (FPN) as compared to the distraction state. In global perspective, during the rumination state, individuals with MDD reflected significantly higher values in explanation ratio, gradient range, and gradient variance along visual-sensorimotor gradient compared to HCs. Finally, we observed significantly reduced correlations between functional connectivity and the primary-transmodal gradient during rumination compared to distraction in HCs. In conclusion, the present study showed that rumination may correspond to a specific underlying functional gradient profile, and such profile was altered in patients with MDD. These results shed new light on the neural mechanisms underlying rumination, highlighting a global functional coupling characteristics across the whole brain during an active rumination state.