Psychotherapy and Neuroscience

Neuroimaging Fear Conditioning

According to neuroimaging findings, fear conditioning’s CS exposure has been significantly linked with increased autonomic response in skin conductance and activations in the amygdala (Cheng, Knight, Smith, Stein, & Helmstetter, 2003; Morris, Buchel, & Dolan, 2001). The trace interval delay periods, i.e. rest periods between US-CS pairings, have been associated with temporally distinct activations in the hippocampus and in the in the anterior midcingulate cortex (aMCC), a structure associated with declared emotion of anxiety (Buchel, Dolan, Armony, & Friston, 1999; Knight, Nguyen, & Bandettini, 2004a). These activations have also been associated with deactivations in more ventral portions of pACC that interestingly have been associated with other emotions of sadness or happiness, a sense of self-reference, and the ability for emotional perspective taking (Hynes, Baird, & Grafton, 2006; Macrae, Moran, Heatherton, Banfield, & Kelley, 2004; Northoff, 2005; Vogt, Berger, & Derbyshire, 2003). Imaging findings reference temporal sequencing of activations during fear conditioning.

To enhance the understanding of regional dissociative functions on conditioning Bechara and colleagues (Bechara, Tranel, Damasio, Adolphs, Rockland, & Damasio, 1995) studied the impact of respective human lesions. They found that a lesion of the amygdala impaired a patient’s acquisition of conditioned autonomic responses of increased skin conductance (Glascher & Adolphs, 2003) to a startling sound but spared the ability to acquire and verbally report task-related declarative facts about task-related stimulus-context relationships (Bechara,et al. 1995). A hippocampal lesion on the other hand impaired a patient’s ability to learn declarative facts, but had no effect on acquisition of the conditioned autonomic response. These findings indicate that the amygdala processes emotional material via its interaction with structures tied to autonomic activity; the hippocampus is involved in the ability for gaining and reporting declarative knowledge about stimulus-context relationships.

In summary, these studies suggest a role for the hippocampus in supporting the processing of fear-related contexts and a role for the amygdala in modulating hippocampal declarative function. They also reflect a functional dissociation between both structures during fear conditioning, whereby the amygdala is involved in CS-US unpairing and linkage to autonomic centers and arousal and the hippocampus in declarative aspects.


Bechara, A., Tranel, D., Damasio, H., Adolphs, R., Rockland, C., & Damasio, A.R. (1995). Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science, 269(5227), 1115-8.

Buchel, C., Dolan, R.J., Armony, J.L., & Friston, K.J. (1999). Amygdala-hippocampal involvement in human aversive trace conditioning revealed through event-related functional magnetic resonance imaging. Journal of Neuroscience, 19(24), 10869-10876.

Cheng, D.T., Knight, D.C., Smith, C.N., Stein, E.A., & Helmstetter, F.J. (2003). Functional MRI of human amygdala activity during Pavlovian fear conditioning: stimulus processing versus response expression. Behavioral Neuroscience, 117(1), 3-10.

Glascher, J., & Adolphs, R. (2003). Processing of the arousal of subliminal and supraliminal emotional stimuli by the human amygdala. Journal of Neuroscience, 23(32), 10274-82.

Hynes, C.S., Baird, A.A., Grafton, S.T. (2006). Differential role of the orbital frontal lobe in emotional versus cognitive perspective-taking. Neuropsychologia, 44(3), 374-383.

Knight, D.C., Nguyen, H.T., & Bandettini, P.A. (2004). Expression of conditioned fear with and without awareness. Proceedings of the National Academy of Sciences U.S.A., 100(25), 15280-3.

Macrae, C.N., Moran, J.M., Heatherton, T.F., Banfield, J.F., & Kelley, W.M. (2004). Medial prefrontal activity predicts memory for self. Cerebral Cortex, 14(6), 647-654.

Morris, J.S., Buchel, C., & Dolan, R.J. (2001). Parallel neural responses in amygdala subregions and sensory cortex during implicit fear conditioning. Neuroimage, 13, 1044-1052.

Northoff, G. (2005). Is emotion regulation self-regulation? Trends in Cognitive Sciences, 9(9), 408-409.

Vogt, B.A., Berger, G.R., & Derbyshire, S.W. (2003). Structural and functional dichotomy of human midcingulate cortex. European Journal of Neuroscience, 18(11), 3134-3144.