Identification of structural disconnection subnetworks in acute and subacute post-stroke depression.

BACKGROUND

Post-stroke depression (PSD) is common after acute ischemic stroke, yet its neural substrates remain unclear. This study identified structural disconnection subnetworks associated with PSD and evaluated their association with depression severity and topology.

METHODS

We retrospectively analyzed 615 first-ever acute ischemic stroke patients. Depressive symptoms were assessed with HAMD-17 at baseline and 3 months. Individual 135 × 135 structural disconnection matrices were constructed from acute DWI lesions (MRI median 3 days post-stroke [1-4]) and HCP-842 normative connectome. Network-Based Statistic (NBS) identified PSD-associated subnetworks; graph theory characterized their topological properties. Partial correlation and linear regression evaluated the association between subnetwork disconnection burden and depression severity.

RESULTS

NBS detected no significant subnetwork in the acute phase. Using identical acute-phase matrices, a cross-hemispheric subnetwork was associated with subacute PSD, centered on the left middle temporal gyrus, bridging the left DMN/limbic system with the right attention, visual, and default mode networks. Total subnetwork disconnection strength independently associated with 3-month HAMD scores (β = 0.001, P = 0.005) after adjusting for baseline depression, neurological deficit, cognition, and lesion volume. The left middle temporal gyrus exhibited the highest degree and betweenness centrality.

CONCLUSIONS

This cross-hemispheric disconnection subnetwork is specifically associated with subacute PSD. The acute-phase negative finding may reflect time-specific phenotypic heterogeneity, where acute-phase PSD represents a mixed syndrome encompassing stress reactions and adjustment disorders, whereas subacute PSD more closely reflects stable structural network injury. This subnetwork provides a connectomic coordinate for understanding PSD-related network disruption and offers a reference for future strategies.