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The Journal of Neuroscience, September 3, 2008, 28(36):9030-9036; doi:10.1523/JNEUROSCI.1651-08.2008

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Behavioral/Systems/Cognitive
Dissociable Roles for the Hippocampus and the Amygdala in Human Cued versus Context Fear Conditioning

Andreas Marschner,¹ Raffael Kalisch,¹ Bram Vervliet,³ Debora Vansteenwegen,² and Christian Büchel¹

¹NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany, ²Department of Psychology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium, and ³Department of Psychology, University of Amsterdam, 1012 WX Amsterdam, The Netherlands

Correspondence should be addressed to Andreas Marschner, NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Email: a.marschner{at}uke.uni-hamburg.de

Lesion studies in animals have identified a critical role of the hippocampus in context fear conditioning. To extend these findings to human volunteers, we used functional magnetic resonance imaging to investigate neural responses associated with context fear conditioning in humans. Our novel conditioning paradigm consisted of aversive electrical shocks (unconditioned stimulus) that were delivered either cue or context related. Differential evoked responses, related to the conditioned stimulus (CS), were found in the anterior cingulate cortex and the bilateral insular cortices, regions that have been implicated in anticipatory anxiety. In case of context conditioning, a similar pattern was observed during the presentation of the entire context. In line with previous conditioning studies, differential responses in the amygdala showed a time by stimulus interaction, suggesting rapid adaptation of CS-specific responses. More importantly, a similar differential decay of activation was observed during context conditioning in the hippocampus, in agreement with a role of the hippocampus in the acquisition phase of human context fear conditioning.

Key words: context; conditioning; hippocampus; amygdala; fMRI; fear

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Received Jan. 22, 2008; accepted July 17, 2008.

Correspondence should be addressed to Andreas Marschner, NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Email: a.marschner{at}uke.uni-hamburg.de

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