Functional connectivity gradients of the insula in major depressive disorder

Introduction: The insula, as a key component of the salience network, plays a crucial role in cognition, emotion regulation, and interoception. Functional abnormalities in the insula have been consistently reported in patients with major depressive disorder (MDD). While prior research has examined functional connectivity gradients in MDD at the whole-brain and network levels, and has characterized insular gradient organization in healthy individuals and related affective disorders, the specific topology of insula functional connectivity gradients in MDD has not yet been directly investigated. This study aimed to reveal the differences in gradient properties of the insula between MDD patients and healthy controls. Methods: Resting-state functional MRI data were collected from 38 MDD patients and 34 age- and gender-matched healthy controls. Functional connectivity gradients were analyzed at three levels: whole-brain, insula-to-whole-brain, and insula-to-seven-brain-networks. Results: At the whole-brain level, the principal gradient distinguished transmodal regions from unimodal regions in both groups. However, the insula-to-whole-brain gradient axis demonstrated a less distinct separation between anterior and posterior insular regions in MDD patients. Additionally, the insula's functional relationship with the dorsal attention network exhibited greater specialization in MDD patients compared to healthy controls. Discussion: These findings extend existing research on insular functional connectivity in depression, highlighting altered gradient properties in MDD. Future research may focus on the relationship between dorsal attention network and insula while taking the laterality of gradients into consideration and assess the reproducibility of the findings.