Functional Connectivity

To assess whether drug effects on amygdala reactivity were part of a wider response within anxiety-relevant amygdala-prefrontal networks, we performed generalized psychophysiological interaction analyses for drug conditions showing significant effects on amygdala reactivity using the generalized psychophysiological interaction toolbox (https://www.nitrc.org/projects/gppi). For each participant, two analyses were performed with the extracted first eigenvariate time courses of the left and right amygdala ROIs, using the same fear versus baseline contrast as the main analyses. Group-level effects were examined using a 2 × 2 analysis of variance with seed hemisphere and drug as factors and head motion as a covariate. To test for effects of the drug, accounting for hemispheric differences, we conducted a t test on the main effect of drug condition. Given a large body of evidence showing modulatory effects of the anterior cingulate cortex on amygdala activity (10) and associations between connectivity in this network and anxiety (11,12), we used an ROI approach with masks taken from the Automated Anatomical Labelling anterior and midcingulate regions. Results were thresholded with a voxelwise threshold of p < .001 uncorrected and a clusterwise threshold of p < .05, FDR corrected within the a priori selected ROI. We also report whole-brain results for completeness.