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

As a prominent psychopathological process of major depressive disorder (MDD), rumination’s brain underpinnings remain unclear. Emerging studies have highlighted that the brain is organized along several macroscale gradients, which could serve as a powerful framework for better understanding how the functional connectome underlies rumination. In this study, we leveraged two datasets (Rum-Beijing and Rum-MDD) to characterize the gradient structure during an active ruminative state. Rum-Beijing consisted of 40 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 investigated the gradient profiles. Several global features of the gradient (range, explanation ratio, variance) and the regional differences of each gradient were also compared. In 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) as compared to the distraction state. We identified replicable altered gradient values in the left dorsolateral prefrontal cortex (DLPFC), superior frontal gyrus (SFG), and posterior cingulate cortex (PCC). Relative to the distraction state, individuals’ gradient range exhibited a replicable and significant reduction along the primary–transmodal gradient, accompanied by a significant increase along the visual–sensorimotor gradient during rumination. Moreover, the MDD group showed a significantly higher primary–transmodal gradient range during the rumination state than HCs. In conclusion, the present study showed that rumination may correspond to a specific underlying functional gradient profile, which was altered in patients with MDD. These results shed new light on the neural mechanisms underlying rumination, highlighting a global functional coupling characteristic across the whole brain during active rumination.