Timing of extinction relative to acquisition: a parametric analysis of fear extinction in humans.

Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans.

[1]  R. Rescorla,et al.  Reinstatement of fear to an extinguished conditioned stimulus. , 1975, Journal of experimental psychology. Animal behavior processes.

[2]  R. Bolles,et al.  Role of conditioned contextual stimuli in reinstatement of extinguished fear. , 1979, Journal of experimental psychology. Animal behavior processes.

[3]  Michael Davis,et al.  Pharmacological and anatomical analysis of fear conditioning using the fear-potentiated startle paradigm. , 1986, Behavioral neuroscience.

[4]  Michael Davis,et al.  Sensitization of the acoustic startle reflex by footshock. , 1989, Behavioral Neuroscience.

[5]  C. Grillon,et al.  Fear-potentiated startle conditioning in humans: explicit and contextual cue conditioning following paired versus unpaired training. , 1997, Psychophysiology.

[6]  C. Grillon,et al.  Fear-potentiated startle in adolescent offspring of parents with anxiety disordersf , 1998, Biological Psychiatry.

[7]  S. Klein,et al.  Handbook of contemporary learning theories , 2000 .

[8]  I. Weiner,et al.  Contemporary Issues in Modeling Psychopathology , 2000, Neurobiological Foundation of Aberrant Behaviors.

[9]  Michael Davis,et al.  Neural Systems Involved in Fear Inhibition: Extinction and Conditioned Inhibition , 2000 .

[10]  E. Foa,et al.  Psychosocial treatment of posttraumatic stress disorder. , 2000, The Journal of clinical psychiatry.

[11]  S. Mineka,et al.  A modern learning theory perspective on the etiology of panic disorder. , 2001, Psychological review.

[12]  C. Grillon,et al.  Contextual fear-potentiated startle conditioning in humans: replication and extension. , 2001, Psychophysiology.

[13]  Michael Davis,et al.  Behavioral and Neural Analysis of Extinction , 2002, Neuron.

[14]  G. Quirk.  Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. , 2002, Learning & memory.

[15]  Christian Grillon,et al.  Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology , 2002, Biological Psychiatry.

[16]  P. Gean,et al.  Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory , 2003, The Journal of Neuroscience.

[17]  K. Kendler,et al.  A twin study of the genetics of fear conditioning. , 2003, Archives of general psychiatry.

[18]  P. Gean,et al.  Involvement of a calcineurin cascade in amygdala depotentiation and quenching of fear memory. , 2003, Molecular pharmacology.

[19]  Christian Grillon,et al.  Anxious responses to predictable and unpredictable aversive events. , 2004, Behavioral neuroscience.

[20]  R. Rescorla,et al.  Spontaneous recovery varies inversely with the training-extinction interval , 2004, Learning & behavior.

[21]  C. Cain,et al.  The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice. , 2005, Learning & memory.

[22]  Tanja Jovanovic,et al.  Fear Potentiation and Fear Inhibition in a Human Fear-Potentiated Startle Paradigm , 2005, Biological Psychiatry.

[23]  O. Van den Bergh,et al.  Reinstatement of fear responses in human aversive conditioning. , 2005, Behaviour research and therapy.

[24]  S. Rauch,et al.  Context modulation of memory for fear extinction in humans. , 2005, Psychophysiology.

[25]  E. Phelps,et al.  Reinstatement of conditioned fear in humans is context dependent and impaired in amnesia. , 2005, Behavioral neuroscience.

[26]  T. Beckers,et al.  Return of fear in a human differential conditioning paradigm caused by a return to the original acquistion context. , 2005, Behaviour research and therapy.

[27]  P. Gean,et al.  Activation of group II metabotropic glutamate receptors induces depotentiation in amygdala slices and reduces fear-potentiated startle in rats. , 2005, Learning & memory.

[28]  Saša Virijević Jovanović,et al.  Contingency awareness and fear inhibition in a human fear-potentiated startle paradigm. , 2006, Behavioral neuroscience.

[29]  Michael Davis,et al.  Different mechanisms of fear extinction dependent on length of time since fear acquisition. , 2006, Learning & memory.

[30]  Michael Davis,et al.  Conditioned fear extinction and reinstatement in a human fear-potentiated startle paradigm. , 2006, Learning & memory.

[31]  R. Bryant,et al.  Extinction Learning Before Trauma and Subsequent Posttraumatic Stress , 2006, Psychosomatic medicine.

[32]  P. Gean,et al.  Extinction Training in Conjunction with a Partial Agonist of the Glycine Site on the NMDA Receptor Erases Memory Trace , 2006, The Journal of Neuroscience.

[33]  Stephen Maren,et al.  Recent fear is resistant to extinction , 2006, Proceedings of the National Academy of Sciences.

[34]  S. Rauch,et al.  Fear extinction in rats: Implications for human brain imaging and anxiety disorders , 2006, Biological Psychology.

[35]  O. Lipp,et al.  Conducting extinction in multiple contexts does not necessarily attenuate the renewal of shock expectancy in a fear-conditioning procedure with humans. , 2007, Behaviour research and therapy.

[36]  Ingie Hong,et al.  Blockade of amygdala metabotropic glutamate receptor subtype 1 impairs fear extinction. , 2007, Biochemical and biophysical research communications.

[37]  Joseph E LeDoux,et al.  Individual differences in fear: isolating fear reactivity and fear recovery phenotypes. , 2007, Journal of traumatic stress.

[38]  Christian Grillon,et al.  Contextual-specificity of short-delay extinction in humans: renewal of fear-potentiated startle in a virtual environment. , 2007, Learning & memory.