Abstract
Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.
Highlights
Interactions between neural structures involved in memory and emotion are fundamental in the adaptation to biologically and socially significant stimuli (LeDoux, 2000)
Pavlovian fear conditioning has been widely used as a model of anxiety disorders (Bouton et al, 2001; Myers & Davis, 2002), human neuroimaging studies have mainly focused on fear conditioning of discrete cues (Buchel et al, 1998; LaBar et al, 1998)
Participants were given a series of painful stimuli, starting with a mild stimulus, which was gradually increased to the level the participants indicated as ‘painful’
Summary
Interactions between neural structures involved in memory and emotion are fundamental in the adaptation to biologically and socially significant stimuli (LeDoux, 2000). After several pairings the neutral cue evokes a phasic fear response and the context evokes a sustained anxiety response (Marks, 1987). Animal research indicates that the amygdala is involved in context and cue conditioning (LeDoux, 2000), whereas the dorsal hippocampus is central only for contextual memory formation (Kim & Fanselow, 1992; Anagnostaras et al, 1999; Rudy et al, 2002). In a positron emission tomography study, Hasler et al (2007) used a cue Received 17 September 2008, revised 1 December 2008, accepted 14 December 2008 and context to induce predictable fear or unpredictable anxiety. Amygdala activation was present only in the predictable and right hippocampal activation in the unpredictable condition, suggesting a unique involvement of the hippocampus in contextual anxiety
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