Right Anterior Insula Hypoactivity During Anticipation of Homeostatic Shifts in Major Depressive Disorder

Objective: To use functional magnetic resonance imaging (fMRI) to examine how shifts in homeostatic state affect anticipatory insular activity in major depressive disorder (MDD). An intact ability to mount preparatory emotional, cognitive, and bodily responses to anticipated environmental change is necessary for adaptive responding. Although abnormal insula activity during aversive anticipation has been observed in individuals with MDD, the extent to which shifts in homeostatic state during anticipation affect insular activity in MDD subjects has not been reported. Methods: Cued hot and warm stimuli were delivered as subjects either passively viewed a fixation cross or performed an attentional task during fMRI. The task was designed so that anticipatory brain activation related to the following three types of shifts could be measured: 1) anticipatory shifts in stimulus intensity; 2) anticipatory shifts in cognitive demand; and 3) dual anticipatory shifts (i.e., shifts in both stimulus intensity and cognitive demand). Brain activation related to each of these three contrasts was compared between 15 (12 females) unmedicated subjects with current MDD and 17 (10 females) age-and education-comparable healthy control (HC) subjects. Results: MDD vs. HC subjects showed lower right anterior insula activity related to anticipatory shifts in stimulus intensity, and altered brain activation during anticipatory shifts in cognitive demand and dual anticipatory shifts. Conclusions: These results indicate that MDD individuals show altered brain responses to shifts in homeostatic state during anticipation, and may suggest that MDD is associated with an impaired ability to effectively prepare for changes in the environment.