The role of hippocampus and amygdala morphology in memory bias of learned fear in youth with chronic pain

Exaggerated recall of pain may pose a risk for pain persistence and elevated pain-related distress. In adults with chronic pain, such discrepancy (or memory bias) has been correlated to hippocampal morphology. However, this has not been examined in youth with chronic pain nor applied to the recall of fear and negative affect, and to amygdala morphology, considering its involvement in threat processing. This study therefore aims to examine whether hippocampal and amygdala shape is related to a biased recall of threat-safety learning in youth with chronic pain. T1-weighted MR images of 85 youth were analyzed (age M=15.6±0.9), of which 54 had chronic pain. The Screaming Lady paradigm was used for threat conditioning. Follow-up memory interviews assessed recalled fear and unpleasantness of conditioned stimuli (threat/CS+, safe/CS-). A discrepancy score was calculated between actual and recalled fear/negative affect (n=60, including n=37 patients). Permutation-based statistics focused on group differences in hippocampus and amygdala morphology using vertex-based shape analysis, as well as on correlations with discrepancy scores (voxel-based thresholding, corrected for multiple comparisons). We found an overall negative memory bias only for unpleasantness of the CS+. On an individual level, 20% had a negatively-biased recall for unpleasantness of the CS+, and 35% for fear of the CS+. Analyses showed no group differences in hippocampal or amygdala shape displacement. Nevertheless, there was a negative correlation between memory bias in fear for the CS+ and right amygdala shape displacement, indicating that a more negative fear-related memory bias is associated with thinning of this region. No other correlations were observed. Our findings revealed that a recall bias for learned fear is related to amygdala morphology in youth. Youth with chronic pain, however, did not differ in amygdala morphology compared to controls. NIH R01HD083270 to LE Simons.