title: Effects of cognitive-behavioral therapy on brain responses to subliminal and supraliminal threat and their functional significance in specific phobia.
abstract: BACKGROUND
  Neurocircuitry models of anxiety disorders suggest dysregulated mechanisms encompassing both automatic and elaborate threat processing. However, the extent to which these processes might be differentially modified by psychotherapy and the neural basis of such changes are unknown. We examined the effects of cognitive-behavioral therapy (CBT) in patients with anxiety disorder on brain responses to subliminal and supraliminal threat.
  
  
  METHODS
  3-Tesla functional magnetic resonance imaging was used to assess neural responses to disorder-related stimuli, presented during two backward-masking conditions employed to manipulate stimulus awareness. In 28 spider-phobic patients randomly assigned to a therapy group or a waiting-list control group scanning was performed before and after completing CBT or a waiting period. Scanning was performed one time in 16 healthy control subjects. Self-report and behavioral measures were used to relate CBT-mediated brain activation changes with symptom improvement.
  
  
  RESULTS
  Untreated patients demonstrated abnormal hyperactivation in the amygdala, fusiform gyrus, insula, anterior cingulate cortex, and dorsomedial prefrontal cortex. Successful CBT was reflected in an overall downregulation in these fear circuitry structures, especially in the right amygdala and anterior cingulate cortex, with reductions in amygdala responsiveness associated with self-reported symptom improvement. However, subliminal threat induced a pattern of right-lateralized hyperactivation in the amygdala and fusiform gyrus that was subject to intersession habituation across groups without showing significant sensitivity to CBT.
  
  
  CONCLUSIONS
  These results challenge prevailing models that emphasize a role for amygdala automaticity in the maintenance of anxiety. Our results suggest CBT-related changes in neural activation associated with fear responses to consciously perceived threat.
authors.affiliation: Department of Biological and Clinical Psychology, Friedrich-Schiller-University Jena, Jena. Electronic address: JLipka@schoen-kliniken.de.
authors.forename: Judith
authors.initials: J
authors.lastname: Lipka
authors.affiliation: Department of Biological and Clinical Psychology, Friedrich-Schiller-University Jena, Jena; Institute of Medical Psychology and Systems Neuroscience, University Hospital Muenster, Muenster, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of Biological and Clinical Psychology, Friedrich-Schiller-University Jena, Jena.
authors.forename: Wolfgang H R
authors.initials: WH
authors.lastname: Miltner
authors.affiliation: Department of Biological and Clinical Psychology, Friedrich-Schiller-University Jena, Jena; Institute of Medical Psychology and Systems Neuroscience, University Hospital Muenster, Muenster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Straube
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D015928:Cognitive Behavioral Therapy; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D010470:Perceptual Masking; D010698:Phobic Disorders / Q000503:physiopathology* / Q000628:therapy*; D010775:Photic Stimulation; D013112:Spiders; D013360:Subliminal Stimulation; D055815:Young Adult
keywords: Anxiety disorder; awareness; cognitive-behavioral therapy; functional magnetic resonance imaging; neural basis of psychotherapy; specific phobia