LAUSR

Physiological hyperarousal is suggested as a core feature of insomnia and resting-state functional magnetic resonance imaging (rs-fMRI) studies have examined the neurobiological basis of the hyperarousal theory. However, few have investigated the associations between rs-fMRI and the biomarkers of physiological hyperarousal. We aimed to investigate (1) the differences in the resting-state functional connectivity (RSFC) between chronic insomnia disorder (CID) patients and good sleepers (GS), and (2) the relationships between altered RSFC and the hyperarousal biomarkers including electroencephalogram (EEG) and heart rate variability (HRV). Fifty CID patients (37 females, 45.8±12.7 years old) and 52 GS (32 females, 37.0±13.2 years old) completed self-report questionnaires, and underwent nocturnal polysomnography and rs-fMRI. We analyzed RSFC in the amygdala (AMYG) and anterior insula (AI), which were core regions of the salience network probably associated with hyperarousal. We also analyzed EEG relative beta power at central derivations and frequency domain HRV parameters (e.g., low frequency and high frequency) in ECG lead ll during sleep. We then tested differences in the RSFC between CID and GS and examined the correlations between RSFC, EEG beta power, and HRV. Compared with GS, CID showed more negative RSFC between the right AMYG and left supramarginal gyrus (SMG), but less positive RSFC between the left AI and bilateral lateral prefrontal cortex (LPFC). The right AMYG-left SMG RSFC was positively correlated with EEG beta power in non-rapid eye movement (NREM) stage 3 sleep measured on central regions (C3: r=-0.336, p=0.012; C4: r=-0.314, p=0.024). We did not find any significant correlations between RSFC and HRV parameters. Decreased RSFC between the AMYG and SMG in insomnia patients may reflect a difficulty in the cortical top-down regulation of the amygdala, indicating hyperarousal during daytime. We also found a significant correlation between the AMYG-SMG RSFC and EEG beta power. This result suggests that altered AMYG connectivity during daytime is associated with cortical hyperarousal during sleep. Overall, our study may provide neurobiological evidence for the 24-hour hyperarousal theory of insomnia. The Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy (study no.: P0014279, 20009210).