Learning about location-dependent threat: neural abnormalities in clinical anxiety

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Anxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to understand the development and maintenance of anxiety disorders. In fMRI, patients with pathological anxiety (ANX, n=23) and healthy controls (HC, n=28) completed a contextual threat learning paradigm in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock). ANX compared with HC showed 1) decreased ventromedial prefrontal cortex and anterior hippocampus activation during the task, particularly in the safe zone, 2) increased insula and dorsomedial prefrontal cortex activation during the task, particularly in the danger zone, and 3) increased amygdala and midbrain/periaqueductal gray activation in the danger zone prior to potential shock delivery. Findings suggest that ANX engage brain areas differently to modulate context-appropriate emotional responses when learning to discriminate cues within an environment.


This research was funded by the Medical Research Council and the Wellcome Trust, United Kingdom. The authors are grateful to the Welcome Trust Centre for Neuroimaging at UCL for providing facilities. We thank the National Institute of Mental Health, UCL Graduate Partnership Program, NIMH T32 grant MH015144, and NIMH K01 MH118428-01 for providing support to B.S.J.


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