0488 Distinct Thalamostriatal Functional Network Dysregulation in Comorbid Insomnia and Sleep Apnea

Abstract Introduction Comorbid insomnia and sleep apnea (COMISA) is a prevalent and distinct phenotype, yet its neural substrates remain poorly defined. Although both insomnia and obstructive sleep apnea (OSA) individually alter brain networks, the combined effect in COMISA has not been systematically examined. We aimed to identify the distinct structural and functional network properties associated with COMISA. Methods We studied 124 male participants (45 controls, 58 OSA, 21 COMISA). Structural covariance networks were derived from cortical thickness data, and functional networks were constructed from resting-state fMRI time-series. Using graph theoretical analysis, we assessed topological properties of weighted, undirected networks, focusing on global metrics (strength, clustering coefficient, efficiency) and nodal metrics (clustering coefficient, closeness centrality). Results Functional networks revealed significantly higher global metrics in both OSA and COMISA groups compared to controls, whereas structural networks showed a nonsignificant trend toward reduced global metrics in patient groups. Crucially, nodal analysis demonstrated that COMISA was distinguished from OSA by significantly higher connectivity (clustering coefficient and closeness centrality) localized to thalamostriatal circuits, including the bilateral thalamus, putamen, and right caudate. The degree of functional alteration correlated with the severity of insomnia and depressive symptoms. Conclusion COMISA is characterized by a unique functional network pattern of thalamostriatal dysregulation, distinct from OSA. These findings suggest that COMISA has a specific neurophysiological basis rooted in dysfunction of subcortical arousal and sleep–wake circuits, offering novel insights into its pathophysiology. Support (if any)