Hierarchical Brain Dynamics Associated With Remission From Major Depression Across Diverse Therapeutic Modalities

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder marked by disrupted brain dynamics. However, the neural mechanisms underlying remission remain poorly understood, particularly regarding common neural markers across diverse therapeutic interventions. Emerging evidence suggests that temporal brain dynamics and their hierarchical organization, referred to as metastates, serve as sensitive markers of individual variability across cognitive functions. In this study, we evaluated whether metastate dynamics derived from resting-state functional magnetic resonance imaging (rs-fMRI) differed according to remission status across pharmacotherapy, psychotherapy, and neuromodulation. METHODS: This multicenter observational study with 370 participants included 229 individuals with depression and 141 healthy control participants. The depression cohort comprised individuals undergoing cognitive behavioral therapy (n = 92), pharmacotherapy (n = 59), electroconvulsive therapy (n = 50), and repetitive transcranial magnetic stimulation (n = 28). rs-fMRI data were analyzed to derive metastate dynamics, and comparisons were made according to remission status across treatment modalities. RESULTS: Two distinct metastates were identified, one associated with higher-order cognitive brain regions and another linked to sensory and motor systems. Participants who achieved remission exhibited greater predictability in transitions between brain states within metastates, supporting higher-order cognitive functions. This altered transition pattern was accompanied by alterations in the anticorrelation between the default mode and executive function networks, which may underlie the increased predictability. CONCLUSIONS: Remission from MDD may involve a reorganization of hierarchical brain dynamics-particularly in systems supporting cognitive control-and may offer a potential treatment modality-independent biomarker of remission.