Human amygdala activation during conditioned fear acquisition and extinction

LaBar, K.S., Gatenby, J.C., Gore, J.C., LeDoux, J.E., & Phelps, E.A. (May 1998). Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron, Vol. 20, 937-945.

The amygdala is believed to be a key component in a network mediating survival functions by coordinating behavioral plans of action based on the integration of exteroceptive and interoceptive information. The amygdala, in particular, has been thought to be the structure responsible for detecting and reacting to potentially threatening environmental stimuli through classical conditioning learning.

However, attempts to investigate amygdala function in humans has produced inconsistent results, with failures to notice increased amygdala blood flow in PET being most surprising. Difficulties may stem from the small size and troublesome subcortical placement of the structure, and that amygdalar responses are relatively transient to discrete cues, have low spontaneous neuronal firing rates, and exhibit marked habituation (gradual signal intensity reduction). This study attempted to overcome these difficulties by using a mixed-trial fMRI design. This time, results successfully showed amygdala/periamygdaloid cortex involvement during both conditioned fear acquisition and extinction, biased towards the right hemisphere in both cases.

Previous lesion studies have shown the integrity of the amygdala is required for expression of learned conditioned fear associations. However, the temporal pattern of amygdala activity (greatest during early acquisition and early extinction, and degrading over time) suggests that this activity may only partially underlie expression. The paper offers a hypothesis that the observed activation may be related to encoding the emotional meaning of the conditioned stimulus. This is consistent with with the amygdala activity witnessed during the initial stages of learning (when stimulus is novel) and during early extinction (when the meaning of the stimulus has changed).