The mediodorsal thalamic nucleus: a critical hub in dysfunctional brain networks of chronic insomnia disorder

STUDY OBJECTIVES: To investigate alterations in functional connectivity of the mediodorsal thalamic nucleus (MD) in chronic insomnia disorder (CID) patients and their correlations with clinical neuropsychological characteristics. METHODS: The study enrolled individuals who met the International Classification of Sleep Disorders-Third Edition criteria for CID, with the addition of age- and sex-matched healthy controls (HCs). Using bilateral mediodorsal medial magnocellular (MDm) and mediodorsal lateral parvocellular (MDl) as seeds, whole-brain resting-state functional connectivity (RSFC) was analyzed. Group RSFC differences between CID and HC were compared, followed by correlations with Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scales, and Self-Rating Depression Scales (SDS) in CID patients. Mediation analyses were conducted to investigate whether RSFC alterations serve as a mediator associated with symptoms of anxiety or depression in CID patients. RESULTS: The study included 50 CID patients and 42 HCs. Patients showed reduced RSFC of the MD with the other subregions of the thalamus, middle frontal gyrus, lingual gyrus, caudate nucleus, and cerebellum. The left MDl-right lingual gyrus connectivity showed a significant negative correlation with Self-Rating Anxiety Scale scores, and this connectivity significantly mediated the relationship between sleep quality and anxiety in CID patients. CONCLUSIONS: Our findings demonstrate that the MD may serves as a critical hub in both sleep-wake regulation and emotional processing networks in CID patients, positioning it as a promising target for personalized neuromodulation therapies aimed at treating CID and its comorbid anxiety. CLINICAL TRIAL: Study on the efficacy and central regulation mechanism of rTMS based on fMRI-guided individualized target in the treatment of chronic insomnia disorder (http://www.chictr.org.cn), ChiCTR2400082526.