Toward an account of clinical anxiety predicated on basic, neurally mapped mechanisms of Pavlovian fear-learning: the case for conditioned overgeneralization

Depress Anxiety. 2012 Apr;29(4):257-63. doi: 10.1002/da.21922. Epub 2012 Mar 23.


The past two decades have brought dramatic progress in the neuroscience of anxiety due, in no small part, to animal findings specifying the neurobiology of Pavlovian fear-conditioning. Fortuitously, this neurally mapped process of fear learning is widely expressed in humans, and has been centrally implicated in the etiology of clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent a unique opportunity to bring recent advances in animal neuroscience to bear on working, brain-based models of clinical anxiety. The current presentation details the neural basis and clinical relevance of fear conditioning, and highlights generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of clinical anxiety. Studies testing such generalization across a variety of anxiety disorders (panic, generalized anxiety disorder, and social anxiety disorder) with systematic methods developed in animals will next be presented. Finally, neural accounts of overgeneralization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anxiety Disorders / pathology
  • Anxiety Disorders / physiopathology*
  • Biomarkers
  • Brain Mapping* / methods
  • Brain Mapping* / psychology
  • Conditioning, Classical / physiology*
  • Fear / physiology*
  • Generalization, Stimulus / physiology*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / psychology
  • Neurons / pathology*
  • Neurons / physiology
  • Predictive Value of Tests


  • Biomarkers