John Cacioppo, PhD2, John Csernansky, PhD1, Xue Wang, PhD3 Left Inferior Frontal Gyrus Links with Negativity Bias in Depressed Women Depression Jackie K. Gollan, PhD1, Megan E. Connolly, PhD1, Angel Buchanan, PhD1, Denada Hoxha, PhD1, Laina Rosebrock, MS1, John Cacioppo, PhD2, John Csernansky, PhD1, Xue Wang, PhD3 1 Northwestern University, Department of Psychiatry and Behavioral Sciences; 2 The University of Chicago, Department of Psychology; 3 Northwestern University Feinberg School of Medicine Department of Radiology Funders: Northwestern Memorial Hospital Womens Board, The Davee Family Foundation ABSTRACT METHODS fMRI Results Whole-brain Analyses. Figure 2 (below) shows areas activated in the whole-brain analyses during the negativity bias condition. The depressed group showed activation in the following areas: middle occipital gyrus (left side), inferior occipital gyrus (left), inferior temporal gyrus (right), and precuneus (left). Conversely, healthy participants activation the following areas: middle occipital gyrus (bilateral), medial part of the superior frontal gyrus, inferior temporal gyrus (right), opercular inferior frontal gyrus (bilateral), and caudate (right) Figure 2. The slice-view image of within group positive and negative whole brain activation. There were no significant differences between group findings (MDD v HV) during the negativity bias condition with uncorrected p < .001. Participants: Female, ages 17-63 years, with DSM-IV Major Depressive Disorder and a score > 23 on the Inventory of Depressive Symptomatology-SR (Rush et al., 2003) (n = 47) and healthy participants (n = 53). No other medical conditions and psychiatric disorders. Measures: The Inventory of Depressive Symptomatology-Clinician and Self-Rated versions (IDS-C and IDS-SR); and an Affective Cognitive Control fMRI task. NB for the behavioral task was calculated as the difference in the mean negative ratings of unpleasant pictures minus the mean positive ratings of pleasant pictures. Imaging data was preprocessed using Matlab and SPM8. Preprocessing included reorientation to the AC- PC, slice timing correction, realignment, coregistration, segmentation, normalization to MNI template, resampling to 2mm isotropic, and smoothing (Gaussian kernel size=6). Background: Negative stimuli evoke a more pronounced and rapid response than equally extreme and arousing positive stimuli, referred to as an affective asymmetry. Despite its importance in processing information, the neural substrates of the negative-positive asymmetry (the ‘negativity bias’) has yet to be studied in women with and without depression. Method: Depressed (n = 26) and healthy participants (n = 26) with very high or low negativity bias completed a clinical interview for DSM-IV Axis I disorders, symptom checklists, a behavioral task to measure the negativity bias. Then, they viewed positive and negative images of social and nonsocial scenes during an event-related fMRI task. Results: Depressed women participants with a higher relative to lower negative bias showed a higher neural activation in the left inferior frontal gyrus. Conclusion: High negativity bias evokes a distinctive pattern of brain activation in the frontal cortex of depressed participants. Increased activation occurred in the left inferior frontal gyrus, which is associated with functions of language and semantic processing, response inhibition, and reappraisal. RESULTS Figure 1. Comparing high and low NB by depression status The main effect demonstrated that participants with high NB exhibited greater activation relative to participants with low NB. This main effect was qualified by a significant interaction, which revealed that NB status did not influence the degree of activation in healthy participants. In contrast, depressed participants with high NB showed greater neural activation than depressed participants with low NB. No significant differences in neural activation between high and low NB groups (ps > .05) in healthy group, but significant difference in the left opercular inferior frontal gyrus in depressed group. INTRODUCTION Negativity bias has been associated with physiological correlates, including a larger late positive evoked potential and an increase of corrugator activity. Negativity bias can also be measured in behavioral tasks across several modalities (e.g., visual, auditory) and types of stimuli (e.g., pictures, words) (Cacioppo et al., 1997). This study investigates compares neural activation of the negativity bias using healthy and depressed women. What areas of the brain are activated, and are there differences between healthy and depressed women when activating the negativity bias? CONCLUSIONS The 2 (NB: high, low) x 2 (diagnosis: MDD, HV) ANOVA showed a main effect of NB (F(1,48) = 5.817, p = .019, η2 = .109), no main effect for diagnosis (F(1,48) = .543, p = .47, η2 = .011), and a significant interaction effect of NB x diagnosis (F(1,48) = 6.068, p = .017, η2 = .112). Relative to healthy women, depressed women with higher negativity bias showed an increased activation in the left inferior frontal gyrus (related to Brodmann area 44), which is associated with language and semantic processing, response inhibition, and cognitive reappraisal. Select References: Cacioppo JT, Gardner WL, Berntson GG (1997): Beyond bipolar conceptualizations and measures: the case of attitudes and evaluative space. Personality and Social Psychology Review 1: 3-25. Jung YC, An SK, Seok JH, Kim JS, Oh SJ, Moon DH, et al. (2006): Neural substrates associated with evaluative processing during co-activation of positivity and negativity: a PET investigation. Biological Psychology 73: 253-261. Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, et al. (2003): The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry 54: 573-583. We welcome your comments, please contact j-gollan@northwestern.edu.