Transition and Dynamic Reconfiguration of Whole-Brain Network in Major Depressive Disorder

Major depressive disorder (MDD) has been characterized by abnormal brain activity and interactions across the whole-brain functional networks. However, the underlying alteration of brain dynamics remains unclear. Here, we aim to investigate in detail the temporal dynamics of brain activity for MDD, and to characterize the spatiotemporal specificity of whole-brain networks and transitions across them. We developed a hidden Markov model (HMM) analysis for resting-state functional magnetic resonance imaging (fMRI) from two independent cohorts with MDD. In particular, one cohort included 127 MDD patients and 117 gender- and age-matched healthy controls, and the other included 44 MDD patients and 33 controls. We identified brain states characterized by the engagement of distinct functional networks that recurred over time and assessed the dynamical configuration of whole-brain networks and the patterns of activation of states that characterized the MDD groups. Furthermore, we analyzed the community structure of transitions across states to investigate the specificity and abnormality of transitions for MDD. Based on our identification of 12 HMM states, we found that the temporal reconfiguration of states in MDD was associated with the high-order cognition network (DMN), subcortical network (SUB), and sensory and motor networks (SMN). Further, we found that the specific module of transitions was closely related to MDD, which were characterized by two HMM states with opposite activations in DMN, SMN, and subcortical areas. Notably, our results provide novel insights into the dynamical circuit configuration of whole-brain networks for MDD and suggest that brain dynamics should remain a prime target for further MDD research.