Negar Fani1, Tricia Z King2, Ryan Brewster2, Amita Srivastava3, Jennifer S Stevens4, Ebony M Glover4, Seth D Norrholm5, Bekh Bradley5, Kerry J Ressler6, Tanja Jovanovic4. 1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: nfani@emory.edu. 2. Department of Psychology, Georgia State University, Atlanta, GA, USA. 3. Morehouse School of Medicine, Atlanta, GA, USA. 4. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. 5. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Atlanta VA Medical Center, Decatur GA, USA. 6. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Abstract
BACKGROUND: Extinction of conditioned fear is an associative learning process that involves communication among the hippocampus, medial prefrontal cortex, and amygdala. Strength of connectivity between the hippocampus and the anterior cingulate cortex (ACC), and between the amygdala and ventromedial prefrontal cortex (vmPFC), may influence fear-potentiated startle (FPS) responses during extinction. Specific white matter tracts, the cingulum and uncinate fasciculus (UF), serve as primary routes of communication for these areas. Our objective was to investigate associations between FPS during extinction and cingulum and UF connectivity. METHOD: Diffusion tensor imaging (DTI) and probabilistic tractography analyses were used to examine cingulum and UF structural connectivity in 40 female African-Americans with psychological trauma exposure. FPS responses during fear conditioning and extinction were assessed via electromyography (EMG) of the right orbicularis oculi muscle. Secondarily, functional connectivity analyses were performed with the seed regions of interest (ROIs) used for tractography. RESULTS: A significant negative association between cingulum microstructure and FPS during early extinction (r = -.42, p = .01) and late extinction (r = -.36, p = .03) was observed after accounting for the effects of age, trauma exposure, and psychopathology (post-traumatic stress disorder symptoms); this pattern was similar for early extinction and functional connectivity between these regions (p < .05(corrected)). No significant correlations were observed between FPS and UF microstructure. CONCLUSIONS: These data indicate that structural integrity of the cingulum is directly associated with extinction learning and appears to influence functional connectivity between these regions. Decrements in cingulum microstructure may interfere with extinction learning, thereby increasing risk for the development of pathological anxiety.
BACKGROUND: Extinction of conditioned fear is an associative learning process that involves communication among the hippocampus, medial prefrontal cortex, and amygdala. Strength of connectivity between the hippocampus and the anterior cingulate cortex (ACC), and between the amygdala and ventromedial prefrontal cortex (vmPFC), may influence fear-potentiated startle (FPS) responses during extinction. Specific white matter tracts, the cingulum and uncinate fasciculus (UF), serve as primary routes of communication for these areas. Our objective was to investigate associations between FPS during extinction and cingulum and UF connectivity. METHOD: Diffusion tensor imaging (DTI) and probabilistic tractography analyses were used to examine cingulum and UF structural connectivity in 40 female African-Americans with psychological trauma exposure. FPS responses during fear conditioning and extinction were assessed via electromyography (EMG) of the right orbicularis oculi muscle. Secondarily, functional connectivity analyses were performed with the seed regions of interest (ROIs) used for tractography. RESULTS: A significant negative association between cingulum microstructure and FPS during early extinction (r = -.42, p = .01) and late extinction (r = -.36, p = .03) was observed after accounting for the effects of age, trauma exposure, and psychopathology (post-traumatic stress disorder symptoms); this pattern was similar for early extinction and functional connectivity between these regions (p < .05(corrected)). No significant correlations were observed between FPS and UF microstructure. CONCLUSIONS: These data indicate that structural integrity of the cingulum is directly associated with extinction learning and appears to influence functional connectivity between these regions. Decrements in cingulum microstructure may interfere with extinction learning, thereby increasing risk for the development of pathological anxiety.
Authors: Ramón J L Lindauer; Miranda Olff; Els P M van Meijel; Ingrid V E Carlier; Berthold P R Gersons Journal: Biol Psychiatry Date: 2005-09-09 Impact factor: 13.382
Authors: Stephen M Smith; Mark Jenkinson; Mark W Woolrich; Christian F Beckmann; Timothy E J Behrens; Heidi Johansen-Berg; Peter R Bannister; Marilena De Luca; Ivana Drobnjak; David E Flitney; Rami K Niazy; James Saunders; John Vickers; Yongyue Zhang; Nicola De Stefano; J Michael Brady; Paul M Matthews Journal: Neuroimage Date: 2004 Impact factor: 6.556
Authors: David C Knight; Christine N Smith; Dominic T Cheng; Elliot A Stein; Fred J Helmstetter Journal: Cogn Affect Behav Neurosci Date: 2004-09 Impact factor: 3.282
Authors: Chien-Lin Yeh; Nina Levar; Hannah C Broos; Alyson Dechert; Kevin Potter; A Eden Evins; Jodi M Gilman Journal: Psychiatry Res Neuroimaging Date: 2019-11-14 Impact factor: 2.376
Authors: Negar Fani; Vasiliki Michopoulos; Sanne J H van Rooij; Cherita Clendinen; Raven A Hardy; Tanja Jovanovic; Barbara O Rothbaum; Kerry J Ressler; Jennifer S Stevens Journal: J Psychiatr Res Date: 2019-05-14 Impact factor: 4.791
Authors: Mackenzie R Riggenbach; Jordan N Weiser; Brianne E Mosley; Jennifer J Hipskind; Leighton E Wireman; Kelsey L Hess; Tessa J Duffy; Julie K Handel; MacKenzie G Kaschalk; Kassidy E Reneau; Boyd R Rorabaugh; Seth D Norrholm; Tanja Jovanovic; Phillip R Zoladz Journal: Behav Brain Res Date: 2019-05-27 Impact factor: 3.332
Authors: Sanne J H van Rooij; Jennifer S Stevens; Timothy D Ely; Rebecca Hinrichs; Vasiliki Michopoulos; Sterling J Winters; Yvonne E Ogbonmwan; Jaemin Shin; Nicole R Nugent; Lauren A Hudak; Barbara O Rothbaum; Kerry J Ressler; Tanja Jovanovic Journal: Biol Psychiatry Date: 2017-09-20 Impact factor: 13.382