Abnormal hypothalamic functional connectivity and serum arousal-promoting neurotransmitters in insomnia disorder patients: a pilot study.

Objective: The present study aimed to investigate the functional connectivity (FC) of the anterior and posterior hypothalamus with the whole brain in insomnia disorder (ID) patients. Additionally, we explored the relationship between FC values and serum levels of arousal-promoting neurotransmitters (orexin-A and histamine) in ID patients.

Methods: This study enrolled 30 ID patients and 30 age- and gender-matched healthy controls. Resting-state functional magnetic resonance imaging (RS-fMRI) was employed to assess the FC of the anterior and posterior hypothalamus with the whole brain. Serum concentrations of orexin-A and histamine were measured using enzyme-linked immunosorbent assay (ELISA). Moreover, Spearman correlation analysis was conducted to investigate the relationship between FC values and serum levels of arousal-promoting neurotransmitters in ID patients.

Results: Our findings showed decreased FC between the posterior hypothalamus and several brain regions including the bilateral orbital superior frontal gyrus, the bilateral angular gyrus, the right anterior cingulate cortex, the left precuneus, and the right medial superior frontal gyrus in ID patients. Additionally, decreased FC was observed between the anterior hypothalamus and the right anterior cingulate cortex among ID patients. Compared to the healthy controls, ID patients showed significantly elevated serum concentrations of orexin-A and histamine. Furthermore, we identified a positive correlation between the FC of the right medial superior frontal gyrus with posterior hypothalamus and histamine levels in ID patients.

Conclusion: ID patients exhibited aberrant FC in brain regions related to sleep-wake regulation, particularly involving the default mode network and anterior cingulate cortex, which may correlate with the peripheral levels of histamine. These findings contribute to our understanding of the potential neuroimaging and neurohumoral mechanism underlying ID patients.