How negative do you feel?

1. VLPFC (L) VLPFC (R) r = 0.62, t = 3.78, p = 0.0008 r = 0.68, t = 4.22, p = 0.0002 Columbia Psychology SCAN Unit http://www.scan.psych.columbia.edu/ SFS SFS Nuc. accumbens Reappraisal Success Which regions? Amygdala VLPFC (L) VLPFC (R) Reappraisal Success Which regions? DMPFC (BA 9) Pre-SMA MFP (BA 10/32) MFP (BA 10/32) SGACC VMPFC/MOFC (BA 25/11) MOFC MFP SGACC FROP DMPFC LOFC VLPFC (R) SGACC VMPFC Anticipation and Stimulus Trial 4 – 7 sec 2.1 sec 4 – 7 sec 4 sec 2 sec 8 sec How negative do you feel? + + + Figure 1 Prefrontal Seed region Unpacking prefrontal function in emotion regulation: fMRI evidence for independent functional pathways through amygdala and nucleus accumbens Tor D. Wager1, Matthew Davidson1, Brent Hughes2, Martin A. Lindquist3, and Kevin N. Ochsner1 1 Department of Psychology, Columbia University; 2 Department of Psychology, University of Texas; 3 Department of Statistics, Columbia University Cognitive & Affective Control Lab http://www.columbia.edu/cu/psychology/tor/ * Download this poster at the website above * Also: Software, results,meta-analysis ROIs Download this poster: http://www.columbia.edu/cu/psychology/tor/ RESULTS INTRODUCTION • 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) Step 1Identify prefrontal seed region of interest Step 2Test pathways in subcortical regions of interest Step 4Identify additional prefrontal regions mediated by amygdala and NAC Activated regions [Reappraise Negative - Look Negative] Regions within active area correlated with reappraisal success Regions of Interest Significant mediators, and path model with both included together NAC (L) Chosen Seed region 0.42 (0.15)** 0.18 (0.09)* NAC VLPFC (R) Reappraisal Success [Neg - Rea] Direct: 0.19 (0.06)* Amy AMY (L) -0.19 (0.06)*** 0.57 (0.17)*** Histogram of bootstrapped Mediation (a*b) effects 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 http://www.columbia.edu/cu/psychology/tor/ ) • STIMULI • Negative and neutral images from the Int’l 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 Color key Whole-brain search Color key Constrained search + - + - q < .01 FDR, P < .0004 P < .005 P < .001 P < .01 q < .05 FDR, P < .0046 P < .05 * = p < .05, ** = p < .01; ***, p < .001, two-tailed SUMMARY and CONCLUSIONS The Mediation Effect Parametric Map analysis, and application to reappraisal data Step 3Identify additional mediators and functional networks MEPM analysis in general: Specify two of the three variables in the path model below Search the third variable over brain voxels, making parametric maps of each effect Bootstrap test provides nonparametric inference MEPM analysis in this case: Specify prefrontal seed (predictor) and reappraisal success (outcome) Search for brain areas in which [Reappraise - Look Negative] mediates the prefrontal activity-success relationship • 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. Mediators of VLPFC-Reappraisal Success connectivity SFS Precuneus Pre-SMA Pre-SMA Thalamus rdACC Caudate vaIns CIs CIs sgACC Amy SFS Mediators: Which brain regions? vStr and sgACC Mediation effect: Significant product of a*b paths. Interpretation: inclusion of indirect path significantly affects predictor-outcome relationship Amygdala Amygdala Indirect Path b Indirect Path a sgACC vStr Amy NAC Hippocampus Control system Activity (Right vlPFC) Reappraisal Success (Drop in reported negative experience) Path b1 a1*b1 distribution Direct Path c’ ANALYSIS PATHWAY Step 1Identify 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 2Test 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 3Identify 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 4Identify 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 < .1 FDR activation and p < .05 correlation in 1 AND 2) Path model with networks as mediators Pre-SMA Precuneus Reappraisal Success NAC/ sgACC CIs Path b1 Path a1 0.24 (0.08)*** 0.66 (0.08)*** Network avg. [Rea - Neg] a1*b1 value Reappraisal Success [Neg - Rea] REFERENCES Total: 0.15 (0.08)* Direct: 0.24 (0.09)* VLPFC (R) See Poster I 64 for a summary of neuroimaging studies of reappraisal Ochsner, K. N., Bunge, S. A., Gross, J. J., & Gabrieli, J. D. E. (2002). Rethinking feelings: An fMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience, 14:8. Mediation analyses of VMPFC-amygdala relationship: (see also work by M. Lieberman): Urry, H. L., van Reekum, C. M., Johnstone, T., Kalin, N. H., Thurow, M.E., Schaefer, H. S., et al. (2006). Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. JNeurosci, 26(16), 4415-4425. Meta-analysis showing brain regions that predict valence of emotional experience: Wager, T. D., Barrett, L. F., Bliss-Moreau, E., Lindquist, K., Duncan, S., Kober, H., et al. (in press). The Neuroimaging of Emotion. In M. Lewis (Ed.), Handbook of Emotion. See also posters A125 and B95 for more on mediation effect parametric mapping See also posters C12, I64, I59, D39 for more on brain representation of emotion Figure 1 Path a2 Path b2 rdACC 0.58 (0.18)*** Path b2 a2*b2 distribution -0.33 (0.11)** Question 1: Does activity in subcortical “affective appraisal systems” mediate the vlPFC-experience relationship? MediationHypothesis: If yes, paths a, b, and their product a*b should be significant Direct pathwayHypothesis: No, only direct path c’ is significant Question 2: If there is mediation, what type of appraisal system does it involve? Negative Mediation: Systems involved in negative affect, like the amygdala Positive Mediation: Systems involved in positive affect, like the striatum Multiple mediation: Multiple, statistically independent mediating regions Subthal. Zone, vPons Reappraisal Success Amy, vaIns * = p < .05, ** = p < .01; ***, p < .001, two-tailed Network avg. [Rea - Neg] a2*b2 value