title: Fear-potentiated startle during extinction is associated with white matter microstructure and functional connectivity.
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.
  
  
  METHODS
  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.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: nfani@emory.edu.
authors.forename: Negar
authors.initials: N
authors.lastname: Fani
authors.affiliation: Department of Psychology, Georgia State University, Atlanta, GA, USA.
authors.forename: Tricia Z
authors.initials: TZ
authors.lastname: King
authors.affiliation: Department of Psychology, Georgia State University, Atlanta, GA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Brewster
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Stevens
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ebony M
authors.initials: EM
authors.lastname: Glover
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Atlanta VA Medical Center, Decatur GA, USA.
authors.forename: Seth D
authors.initials: SD
authors.lastname: Norrholm
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Atlanta VA Medical Center, Decatur GA, USA.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
mesh_terms: D000328:Adult; D001741:Black or African American; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology; D056324:Diffusion Tensor Imaging; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D013216:Reflex, Startle / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology / Q000503:physiopathology*; D066127:White Matter / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
keywords: Anterior cingulate cortex; Cingulum; Connectivity; Extinction; Fear-potentiated startle; Hippocampus