A multicenter cross-sectional study to elucidate altered resting-state functional connectivity of the insular cortex in anorexia nervosa, segmented by functional localization.

Although changes in insular function have been thought to play a central role in the pathophysiology of anorexia nervosa (AN), due to factors such as insufficient sample size, there have been no studies examining changes in resting-state functional connectivity (rsFC) between insula and whole brain in AN, based on functional localization of insula. Here, we subdivided insula into 6 regions per side based on functional localization and reanalyzed previously published functional magnetic resonance imaging data from 114 female patients with AN and 135 female healthy controls (HC). We calculated the rsFCs between ROIs and compared the results between groups, with the 12 insular regions serving as seed ROIs and 142 regions of the whole brain as target ROIs. Compared to HC, AN patients had a increased rsFC between dorsal anterior insula (daIC) and amygdala, and a decreased rsFC between posterior division of dorsal middle insula (pdmIC) and opercular cortex (false discovery rate [FDR] corrected p-value < 0.05 with analysis-level correction, which means that FDR correction was applied to all seed ROIs and all target ROI combinations). These rsFC changes may be the neurological basis for AN symptoms, such as hypersensitivity to negative stimuli, taste disorder, and enhanced taste aversion learning.