Abstract Introduction This study aimed to explore the brain functional patterns associated with frequent nighttime awakenings in patients with comorbid insomnia and obstructive sleep apnea (COMISA) to further elucidate the underlying regulatory mechanisms. Methods A total of 99 participants were enrolled between March 2024 and February 2025, including individuals with COMISA, insomnia, or obstructive sleep apnea (OSA), as well as healthy controls. All participants underwent demographic and clinical assessments, polysomnography, and brain MRI. MRI metrics were compared across groups, followed by correlation and regression analyses with the arousal index. Results Patients with COMISA exhibited more severe insomnia, poorer sleep quality, and greater impairment in daytime functioning. Nocturnal awakenings were more frequent in COMISA than that in insomnia, even after excluding regular hypnotic users. Furthermore, patients with COMISA showed altered activity in the right inferior frontal gyrus, opercular part (IFGoperc. R), left middle temporal gyrus (MTG. L), and right cerebellar lobule VIII (Cerebellum₈R). Functional connectivity (FC) analyses revealed that, within the cerebellum, COMISA patients had stronger FC between the lobule IV-V and the right angular gyrus (ANG. R), but lower FC between the left lobule IX and the left medial orbital superior frontal gyrus (ORBsupmed. L), compared with patients with insomnia. Correlation analyses indicated that the arousal index was positively associated with body mass index (BMI), hypertension history, apnea-hypopnea index (AHI), and several FC or degree centrality (DC) measures, and negatively associated with gender, years of education, and the fractional amplitude of low-frequency fluctuation (fALFF) value of the Cerebellum₈R. Further regression analysis showed that the fALFF value of Cerebellum₈R was independently associated with nocturnal arousal. This association remained significant after adjusting for insomnia severity and sleep efficiency. Conclusion This study demonstrated that patients with COMISA experienced more frequent nocturnal arousal than those with insomnia. Reduced functional activity in Cerebellum₈R was independently associated with increased arousal, even after adjusting for insomnia severity, suggesting a potential role in the neural regulation of nocturnal awakenings. These findings highlight a potential neural target that may complement conventional treatments for nocturnal arousal (Registration No.: ChiCTR 2500095809). Support (if any) We acknowledge the International Sleep Research Training Program of the World Sleep Society.
Zhang et al. (Fri,) studied this question.