+ How negative do you feel? 2 sec 4 sec 8 sec 4 7 sec2.1 sec4 7 sec Anticipation and Stimulus Trial + + Figure 1Columbia Psychology SCAN Unit INTRODUCTION METHODS PARTICIPANTS n = 36 participants, mean age = 22 years SCAN & ANALYSIS PARAMETERS EPI BOLD imaging on 1.5T GE (TR = 2 s, 31 slices 3.5 x 3.5 x 4.5 mm voxels). Pre-processing and 1st level analysis with SPM2 2nd-level analysis using MEPM toolbox (beta version available from) STIMULI Negative and neutral images from the Intl Affective Picture System (IAPS) TRIAL TYPES Reappraise Negative Images = Instructed regulation Look at Negative Images = Spontaneous responses, which could include regulation of emotion Look at Neutral Images = Spontaneous responses to neutral events TRIAL STRUCTURE BACKGROUND The capacity to adaptively regulate emotion is essential for both mental and physical health. Recent imaging research has identified regions of PFC important for the goal-directed reappraisal of aversive stimuli (Beauregard et al., 2001; Ochsner et al., 2002; Phan et al., 2004; Urry et al., 2006) These studies have identified both cortical and subcortical activation related to cognitive reappraisal of emotion, but they have not systematically identified cortical-subcortical pathways. QUESTION In this study, we sought to investigate cortical-subcortical pathways that predict self-reported reappraisal success. We used a novel strategy of mediation effect parametric mapping (MEPM) to locate subcortical mediators of observed prefrontal- reappraisal success relationships. (see also posters A125 and B95) RESULTS SUMMARY and CONCLUSIONS Step 1: Bilateral VLPFC and other prefrontal regions are correlated with reported success when reappraising aversive pictures. Step 2: The relationship between VLPFC activity and success is mediated by statistically separable pathways through amygdala and NAC. Activation of the amygdala pathway predicts lower reappraisal success (more negative emotion), and activation of the NAC pathway predicts greater success. VLPFC is positively associated with both pathways, implying a role in both up- and down-regulation of emotion by appraisal. Step 3: Two separate networks of mediators connected to VLPFC were found. The positive mediation network involved NAC, pre-SMA, retrosplenial cortex and precuneus, and was associated with greater success. The negative mediation network involved rostral, dorsal cingulate, amgydala, subthalamus, and pons, and was associated with lower success. Step 4: Several other frontal regions, including dorsal and ventral medial PFC, also showed relationships with reappraisal success mediated by NAC. However, only right VLPFC and orbitofrontal cortex showed relationships with success mediated by amygdala. REFERENCES ANALYSIS PATHWAY Step 1 Identify prefrontal seed region of interest. Used contrasts to identify regions involved in instructed reappraisal (Reapp Neg > Look Neg) that were a) activated and b) correlated positively with reappraisal success. Defined right VLPFC as prefrontal seed region. Step 2 Test pathways in subcortical regions of interest. Defined regions of interest around amygdala and ventral striatum/nuc. Accumbens (NAC). Conducted mediation analyses (MEPM) for voxels in these regions. See Step 2 Hypotheses at right. Step 3 Identify additional mediators and functional networks to which they belong. Purpose: Big picture understanding of networks constrains inference. Performed MEPM analysis over whole brain, searching for other mediators. Used hierarchical clustering and permutation test to group regions into networks, and examine mediation on network averages. Step 4 Identify additional prefrontal regions mediated by amygdala and NAC. Purpose: Move beyond single prefrontal ROI to examine big picture in frontal cortex. Identified regions involved in both spontaneous and instructed regulation (P