The role of the orbitofrontal cortex in anxiety disorders

Ann N Y Acad Sci. 2007 Dec;1121:546-61. doi: 10.1196/annals.1401.006. Epub 2007 Aug 14.


Advances in neuroimaging techniques over the past two decades have allowed scientists to investigate the neurocircuitry of anxiety disorders. Such research has implicated the orbitofrontal cortex (OFC). Characterizing the role of OFC in anxiety disorders, however, is principally complicated by two factors-differences in underlying pathophysiology across the anxiety disorders and heterogeneity in function across different OFC sub-territories. Contemporary neurocircuitry models of anxiety disorders have primarily focused on amygdalo-cortical interactions. The amygdala is implicated in generating fear responses, whereas cortical regions, specifically the medial OFC (mOFC) and the ventromedial prefrontal cortex (vmPFC), are implicated in fear extinction. In contrast to mOFC, anterolateral OFC (lOFC) has been associated with negative affects and obsessions and thus dysfunctional lOFC may underlie different aspects of certain anxiety disorders. Herein, we aim to review the above-mentioned theories and provide a heuristic model for conceptualizing the respective roles of mOFC and lOFC in the pathophysiology and treatment of anxiety disorders. We will also review the role of the OFC in fear extinction and the implications of this role to the pathophysiology of anxiety disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anxiety Disorders / pathology
  • Anxiety Disorders / physiopathology*
  • Anxiety Disorders / psychology*
  • Frontal Lobe / pathology
  • Frontal Lobe / physiopathology*
  • Humans