Neuroimaging insights into default mode network alterations following dexmedetomidine-controlled sleep in insomnia patient comorbid with depression

Objectives To investigate alterations in small-world network properties and functional connectivity within the default mode network (DMN) in treatment-responsive patients with chronic insomnia disorder (CID) comorbid with major depressive disorder (MDD), following patient-controlled sleep therapy (PCSL) with Dexmedetomidine (Dex-PCSL). Methods Fifty-two CID patients comorbid with MDD who responded to Dex-PCSL underwent pre- and post-treatment clinical assessments and MRI scans. Fifty-six age- and sex-matched healthy controls were also recruited. Clinical measures included the Pittsburgh Sleep Quality Index (PSQI), the 17-item Hamilton Depression Rating Scale (HAMD-17), and actigraphy-based sleep metrics. Graph theory analyses were first applied to evaluate small-world network properties at the whole-brain level, and functional connectivity analyses were then performed within the DMN to assess treatment-related changes. Results At baseline, patients exhibited disrupted small-world properties and globally reduced functional connectivity within the DMN. After therapy, neuroimaging revealed marked changes, including the number of weakened connections within DMN subsystems decreased, while new, enhanced functional connections emerged between brain regions. Small-world network metrics improved, as indicated by increased clustering coefficient (Cp) and decreased shortest path length (Lp), and its elevation correlated with improved sleep efficiency. Conclusion Dex-PCSL improves small-world properties and restores functional connectivity within the DMN in CID patients comorbid with MDD, with these network reorganizations closely associated with enhanced sleep efficiency.