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Abstract:
Mental disorders such as major depressive disorder (MDD) are characterized by imbalances in homeostatic processes, which is reflected in altered neural function at rest. The insula has been proposed as a key region in regulating homeostasis. Within the insular cortex, distinct subregions have been associated with predictive or evaluative coding of homeostatic states, respectively, but it is still largely elusive if functional segregation is specifically impaired in MDD patients. To test for loss of specificity within functional connectivity (FC) profiles of insular subregions in MDD, we measured resting-state fMRI in 432 MDD patients and 418 healthy controls. We tested specificity by comparing the similarity between 6 sub-regional, insular FC profiles for MDD and healthy controls using Pearson correlation. As expected, MDD patients showed a greater similarity in FC profiles of insular subregions compared to healthy control participants (t = -4.31; p < .001) suggesting lower functional segregation. Critically, this difference in similarity was specific to the insular cortex as comparing FC profiles of 6 subregions within the temporal cortex yielded no significant interaction effect (t = -1.37; p = .17). Thus, our results corroborate the hypothesized loss of functional segregation within the insula. We conclude that an increased reliance on interoceptive predictions and a discounting of exteroceptive signals might contribute to the pathophysiology in MDD.
