Distinct alterations of functional connectivity of the basal forebrain subregions in insomnia disorder

Cholinergic basal forebrain (BF) plays an important role in sleep-wake regulation and is implicated in cortical arousal and activation. However, less is known currently regarding the abnormal BF-related neuronal circuit in human patients with insomnia disorder (ID). In this study, we aimed to explore alterations of functional connectivity (FC) in subregions of the BF and the relationships between FC alterations and sleep and mood measures in ID.

One hundred and two ID patients and ninety-six healthy controls (HC) were included in this study. Each subject underwent both resting-state fMRI and high-resolution anatomical scanning. All participants completed the sleep and mood questionnaires in ID patients. Voxel-based resting-state FC in each BF subregion (Ch_123 and Ch_4) were computed. For the voxel-wise FC differences between groups, a two-sample t-test was performed on the individual maps in a voxel-by-voxel manner. To examine linear relationships with sleep and mood measures, Pearson correlations were calculated between FC alterations and sleep and mood measures, respectively.

The ID group showed significantly decreased FC between the medial superior frontal gyrus and Ch_123 compared to HC. However, increased FC between the midbrain and Ch_4 was found in ID based on the voxel-wise analysis. The correlation analysis only revealed that the altered FC between the midbrain with Ch_4 was significantly negatively correlated with the self-rating anxiety scale.

Our findings of decreased FC between Ch_123 and medial superior frontal gyrus and increased FC between midbrain and Ch4 suggest distinct roles of subregions of BF underlying the neurobiology of ID.