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Neuroprogression of chronic stress-induced depression via longitudinal fMRI

Year: 2026
Type: article
Abstract: Background: 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. Methods: 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. Results: 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. Conclusion: 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.
DOI: 10.3389/fpsyt.2026.1898694
Language: English
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221830185
FWCI:
Cites: 89
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Related to: 10