Psychotherapy and Neuroscience

Extinction-Animal Research

Fear-related extinction evolves when a fear producing CS or context is presented in absence of a US to cause its learned unpairing. Extinction learning reflects a CS-no US fear association (or CR-no fear) association superimposed on a fear producing CS-fear (or CR-fear) association (Garcia, 2002; Vianna et al., 2004). Extinction does not evolve from disuse and is not equivalent to forgetting. Therefore, the mere passage of time is not sufficient for extinction to occur, but reexposure to the actual CS without the aversive stimulus is required until the CR disappears.

Extinction is reflective of cortical inhibition of stress arousal (Pitman, Shalev, & Orr, 2000). It is mediated by discrete brain regions like the medial prefrontal cortex (mPFC). With the start of extinction training (i.e. unpairing CS) this region’s neurons incrementally increase neural activity. Neural activity in this region has been positively correlated with reduced fear reactivity and negatively correlated with fear induced freezing behaviors (Milad & Quirk, 2002). According to neurophysiological recordings in the rodent, this region’s neurons are very sensitive to the presence of aversive stimuli. MPFC neurons reactively reduce and depress spontaneous activity to conditioned fear stimuli in response to fear induced abnormal amygdala modulation (Garcia, Vouimba, Baudry, & Thompson, 1999; Herry & Mons, 2004). Medial PFC lesions prior to fear conditioning impair the later development of extinction (Morgan, Romanski, & LeDoux, 1993). Interestingly post-training lesions have marginal effects on extinction training but significantly impair extinction training performance after the later spontaneous recovery of fear conditioning (Morgan, Schulkin, & LeDoux, 2003). These findings suggest that an intact mPFC is needed at the time of fear conditioning’s acquisition to allow for the later expression of extinction. These findings also suggest a role for the mPFC in the early acquisition phase of fear conditioning learning; its activity and influence persist throughout the extinction phase.


Garcia, R. (2002). Post-extinction of conditioned fear: between two CS-related memories. Learning and Memory, 9(6) 361-3.

Garcia, R., Vouimba, R.M., Baudry, M., & Thompson, R.F. (1999). The amygdala modulates prefrontal cortex activity relative to conditioned fear. Nature, 402(6759), 294-296.

Herry, C., & Mons, N. (2004). Resistance to extinction is associated with impaired immediate early gene induction in medial prefrontal cortex and amygdala. European Journal of Neuroscience, 20(3), 781-790.

Milad, M.R., & Quirk, G.J. (2002). Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 420(6911), 70-74.

Morgan, M.A., Romanski, L.M., & LeDoux, J.E. (1993). Extinction of emotional learning. Contribution of medial prefrontal cortex. Neuroscience Letters, 163, 109-113.

Morgan, M.A., Schulkin, J., & LeDoux, J.E. (2003). Ventral medial prefrontal cortex and emotional perseveration: the memory for prior extinction training. Behavioral Brain Research, 146(1-2), 121-130.

Pitman, R.K., Shalev, A.Y., & Orr, S.P. (2000). Post-traumatic stress disorder: emotion, conditioning, and memory. In: M.S. Gazzaniga (Ed.), The cognitive neurosciences, 2nd ed. (pp. 1133-1148). Cambridge, MA: MIT Press.

Vianna, M.R., Coitinho, A., & Izquierdo, I. (2004). Role of the hippocampus and amygdala in the extinction of fear-motivated learning. Current Neurovascular Research, 1, 55-60.