Aberrant Functional Connectivity of Basal Forebrain Subregions with Cholinergic System in Short-term and Chronic Insomnia Disorder

To systematically investigate structural and functional abnormalities in subregions of the basal forebrain (BF) using structural and resting-state fMRI, and to examine their clinical relevance in short-term and chronic insomnia disorder (ID). Thirty-four patients with short-term ID, 41 patients with chronic ID, and 46 healthy controls (HCs) were recruited. Grey matter volume and seed-based resting-state functional connectivity (RSFC) in each BF subregion (Ch1,2,3 and 4) were computed and compared among the three groups. Spearman correlation was used to estimate the relationships between MRI-based alterations and clinical variables. The short-term group exhibited lower RSFC with the bilateral striatum and bilateral Ch_4 than HCs and the chronic group. In the left Ch_4, subjects in the chronic group exhibited lower RSFC with the left middle cingulate cortex than HCs and the short-term group. The short-term group exhibited lower RSFC with the left parahippocampal gyrus (PHG) than HCs and the chronic group. The chronic group exhibited the highest RSFC with the left middle frontal gyrus (MFG), followed by HCs and the short-term group. In the right Ch_4, the chronic group exhibited the lowest RSFC with the right superior temporal gyrus, followed by HCs and the short-term group. Moreover, in the short-term group, negative correlations were found between the left Ch_4 and left MFG RSFC and Epworth Sleepiness Scale scores. These findings suggest that the Ch_4 may be a key node for establishing diagnostic and categorical biomarkers of ID, which could be useful in developing more effective treatment strategies for insomnia.