Journal
PSYCHOLOGICAL MEDICINE
Volume 44, Issue 2, Pages 381-394Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0033291713000792
Keywords
fMRI; fear conditioning; defensive reaction; panic disorder; midbrain; Agoraphobia; frontal cortex
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Funding
- German Federal Ministry of Education and Research (BMBF) as part of the BMBF Psychotherapy Research Funding Initiative [01GV0615, 01GV0611]
- Ethics Committee of the Medical Faculty of the Technische Universitat Dresden [EK 164082006]
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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. Method 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.
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