Brain functional connectome of rumination in patients with major depressive disorder

Abstract

Rumination in major depressive disorder (MDD) is defined as persistent and passive focus on negative self-relevant information, depressive symptoms, and its causes and consequences. Rumination encompasses various cognitive and emotional subprocesses linked with activation in diverse brain areas, such as self-referential processing, autobiographical memories recalling, and emotional processing/regulation. The brain functional connectome offers a possible tool to map the neural basis of rumination as an intact regime and anatomize the organization neural dynamic associated with rumination. Thus, this thesis aims to detangle the neural basis of rumination from a functional connectome perspective in patients with MDD. Study 1 utilized a longitudinal design of 6–10 weeks. The results indicated that MDD patients with high tendency for rumination are predisposed to experience lesser changes in depressive symptoms than those with low rumination tendency, which further confirmed the role of rumination in prolonged depressive severity in MDD. Study 2 sought to detangle the ruminative neural network organizational profile in the healthy state and the specific pattern under depressive state indicated by MDD. Under the rumination context, brain areas in the posterior part of the default mode network, visual mental imagery, and emotional processing are largely engaged (Study 2a). These active regions are defined as the ruminative neural network. Subsequently, we constructed a ruminative functional connectome and estimated the network topological properties using graph theory. The metric tapping functional integration (e.g., global efficiency) and segregation (e.g., local efficiency) indicate the disorganization of the patterns of network metrics of the ruminative neural network. Moreover, regions exhibiting disrupted nodal centralities are located in the default mode network, emotional processing, visual mental imagery, and attentional control systems. Study 3 considered anhedonia, which is close to rumination, might result from perturbations to the orchestration of state transitions. As an essential property of neural activity linking brain structure and function connectivities, metastability is a measure of the variation on the states of phase synchrony as a function of time. Our exploration of the profile of metastability in MDD and its relationship with rumination found that MDD intends to linger in a state with higher global synchronization and lesser metastability than the controls. We investigated further whether white matter microstructure integrity deficits (accessed by diffusion tensor imaging) are associated with metastability. Accordingly, decreased metastability was found to be closely associated with white matter microstructure integrity in the genu of the corpus callosum interconnecting bilateral prefrontal areas. Moreover, an anomalous brain state is a predictor forecasting the rumination level and attention lapse in MDD. The research domain criteria framework suggests that detangling rumination is a window to understanding the neuropathological mechanism of depression. Current study fusing different modality data from connectome perspective on rumination is predicted to further knowledge on guiding diagnostic and treatment planning decisions in MDD.