RT Journal Article SR Electronic T1 Valence-dependent coupling of prefrontal-amygdala effective connectivity during facial affect processing JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0079-19.2019 DO 10.1523/ENEURO.0079-19.2019 A1 David Willinger A1 Iliana I. Karipidis A1 Selina Beltrani A1 Sarah V. Di Pietro A1 Ronald Sladky A1 Susanne Walitza A1 Philipp Stämpfli A1 Silvia Brem YR 2019 UL http://www.eneuro.org/content/early/2019/07/09/ENEURO.0079-19.2019.abstract AB Despite the importance of the prefrontal-amygdala network for emotion processing, valence-dependent coupling within this network remains elusive. In this study, we assessed the effect of emotional valence on brain activity and effective connectivity. We tested which functional pathways within the prefrontal-amygdala network are specifically engaged during the processing of emotional valence. Thirty-three healthy adults were examined with functional magnetic resonance imaging while performing a dynamic faces and dynamic shapes matching task. The valence of the facial expressions varied systematically between positive, negative, and neutral across the task. Functional contrasts determined core areas of the emotion processing circuitry, comprising the medial prefrontal cortex (MPFC), the right lateral prefrontal cortex, the amygdala and the right fusiform face area. Dynamic causal modelling demonstrated that the bidirectional coupling within the prefrontal-amygdala circuitry is modulated by emotional valence. Additionally, Bayesian model averaging showed significant bottom-up connectivity from the amygdala to the MPFC during negative and neutral, but not positive, valence. Thus, our study provides strong evidence for alterations of bottom-up coupling within the prefrontal-amygdala network as a function of emotional valence. Thereby our results not only advance the understanding of the human prefrontal-amygdala circuitry in varying valence context, but, moreover, provide a model to examine mechanisms of valence-sensitive emotional dysregulation in neuropsychiatric disorders.Significance statement Recent neuroimaging studies have emphasized the importance of valence-sensitivity within the prefrontal-amygdala network during emotion processing. Yet, it remains elusive which specific pathways are involved in processing affective information, and how this information is integrated in the brain’s network. In particular, the amygdala’s role in signaling valence information to the cortex is subject to ongoing discussions. Moreover, as aberrant brain function has been found in the amygdala and the prefrontal cortex in various debilitating psychiatric disorders, understanding the mechanisms of processing emotional stimuli with different valence (positive, negative, neutral) is particularly relevant for the field. Our findings indicate changes in coupling strength as a function of emotional valence within the prefrontal-amygdala network.