Neuroprogression of chronic stress-induced depression via longitudinal fMRI.
Authors
Affiliations (3)
Affiliations (3)
- Department of Systems Science, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, China.
- International Academic Center of Complex Systems, Beijing Normal University, Zhuhai, China.
- School of Systems Science, Beijing Normal University, Beijing, China.
Abstract
Depression is increasingly viewed as a progressive neurobiological trajectory, yet the spatiotemporal transition from early mood dysregulation to chronic network failure, and its relation to disease-related functional decline, remains unclear. Using a chronic unpredictable mild stress (CUMS) mouse model, we aimed to map the longitudinal brain transformation from local spontaneous activity to global network dysfunction via multi-parametric MRI. Longitudinal functional magnetic resonance imaging (fMRI) was performed on a cohort of CUMS mice (n = 7) across three longitudinal time points: Day 0 (baseline), Day 5 CUMS, and Day 10 CUMS. We integrated four analytical approaches: fALFF, static functional connectivity, graph theory, and dFC/dALFF. Depression progression followed a hierarchical spatiotemporal dissolution. fALFF revealed sequential breakdown of local hubs in caudoputamen, medial prefrontal cortex, and hippocampus, suggesting involvement of motor-motivational and executive deficits. sFC showed sensory-limbic uncoupling between caudoputamen and visual areas, and altered mPFC-AON connectivity and hippocampal prefrontal (HPF-PL) dysconnectivity, indicating limbic-olfactory loop disruption. Graph theory indicated preserved global node efficiency but widespread loss of node local efficiency and clustering. Dynamic analyses uncovered a shift from flexible network reconfiguration to dynamic rigidity. Longitudinal CUMS exposure was associated with progressive alterations in functional network organization. The prefrontal olfactory dysconnectivity and onset of dynamic rigidity represent candidate multi-scale and longitudinal imaging features that warrant future validation.