title: Brain activation during fear extinction predicts exposure success.
abstract: Exposure therapy, a gold-standard treatment for anxiety disorders, is assumed to work via extinction learning, but this has never been tested. Anxious individuals demonstrate extinction learning deficits, likely related to less ventromedial prefrontal cortex (vmPFC) and more amygdala activation, but the relationship between these deficits and exposure outcome is unknown. We tested whether anxious individuals who demonstrate better extinction learning report greater anxiety reduction following brief exposure.
  
  
  
  Twenty-four adults with public speaking anxiety completed (1) functional magnetic resonance imaging during a conditioning paradigm, (2) a speech exposure session, and (3) anxiety questionnaires before and two weeks postexposure. Extinction learning was assessed by comparing ratings to a conditioned stimulus (neutral image) that was previously paired with an aversive noise against a stimulus that had never been paired. Robust regression analyses examined whether brain activation during extinction learning predicted anxiety reduction two weeks postexposure.
  
  
  
  On average, the conditioning paradigm resulted in acquisition and extinction effects on stimulus ratings, and the exposure session resulted in reduced anxiety two weeks post-exposure. Consistent with our hypothesis, individuals with better extinction learning (less negative stimulus ratings), greater activation in vmPFC, and less activation in amygdala, insula, and periaqueductal gray reported greater anxiety reduction two weeks postexposure.
  
  
  
  To our knowledge, this is the first time that the theoretical link between extinction learning and exposure outcome has been demonstrated. Future work should examine whether extinction learning can be used as a prognostic test to determine who is most likely to benefit from exposure therapy.
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Tali Manber
authors.initials: TM
authors.lastname: Ball
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Knapp
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.|Laureate Institute for Brain Research, Tulsa, OK, USA.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.|Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.|Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D001921:Brain / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D007171:Implosive Therapy / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
keywords: SAD/social anxiety disorder/social phobia; anxiety/anxiety disorders; behavior therapy; brain imaging/neuroimaging; functional MRI; phobia/phobic disorders