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Functional Magnetic Resonance Imaging Signature of Pain Anticipation and Clinical Depressive Symptomatology


Using functional magnetic resonance imaging (fMRI), this study tested the hypothesis that individuals diagnosed with major depressive disorder (MDD) are more likely to anticipate negative outcomes. The participants included thirty-one (15 females) unmedicated adults diagnosed with MDD and twenty-two (11 females) healthy control subjects with no history of MDD. fMRI data were collected during an event-related pain-anticipation paradigm, during which participants were cued to anticipate painful heat stimuli. Stimuli were delivered at high (moderately painful sensation) or low (mild painful sensation) intensity, and all cues were either known (high and low pain cues), or unknown (50% probability of high or low pain, which was not known to the participant), with a total of fourteen known and fourteen unknown anticipation trials. Based on prior findings regarding the importance of the insula cortex during pain anticipation, twelve insular regions (six on each side) were examined. Single-subject multi-voxel pattern analysis (MVPA) was used to create subject-specific activation maps for each anticipation condition. The mean activation (beta coefficient) was extracted within each insular region and was subjected to linear regression by way of a least absolute shrinkage and selection operator (LASSO). Following LASSO regression, prediction analysis was conducted on the test set (activation maps from fourteen unknown anticipation trials), based on the correlation with the training set (activation maps from fourteen known anticipation trials). Across each unknown anticipation trial, participants’ anticipation was classified as either high pain (HP) or low pain (LP). Several results were observed. First, we found that, within the chosen insular regions, neurobiological signatures of high and low pain anticipation were distinguishable at a high sensitivity. Second, the anterior short gyrus on the right side showed the highest deterministic beta coefficient in anticipatory predictions in our study. Third, we found that across both groups more of the unknown anticipatory conditions were labeled as HP. Fourth, in the current sample, we found no significant relationship with overall depressive symptoms severity and anticipatory labeling. Nevertheless, as hypothesized, significantly more cases of unknown anticipation were labeled as HP in the depressed cohort than in the control group (chi= 3.9; p < 0.05).

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