title: Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia.
abstract: BACKGROUND
  Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients.
  
  
  METHODS
  The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls.
  
  
  RESULTS
  Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.
  
  
  CONCLUSIONS
  The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.
authors.affiliation: Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Lueken
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Straube
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Reinhardt
authors.affiliation: Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: N I
authors.initials: NI
authors.lastname: Maslowski
authors.affiliation: Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Germany.
authors.forename: H-U
authors.initials: HU
authors.lastname: Wittchen
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ströhle
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wittmann
authors.affiliation: Department of Clinical Radiology, University of Münster, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Pfleiderer
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Konrad
authors.affiliation: Department of Clinical Radiology, University of Münster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ewert
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Uhlmann
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Jansen
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kircher
mesh_terms: D000328:Adult; D000379:Agoraphobia / Q000453:epidemiology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology; D015897:Comorbidity; D003213:Conditioning, Psychological / Q000145:classification / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000453:epidemiology / Q000503:physiopathology*