Abstract:

Pavlovian fear conditioning, a form of associative learning, was used to examine contextually modulated reinstatement of extinguished fear. The aim of two studies was to improve understanding of the role of autonomic and declarative memory systems in fear reinstatement in humans, and, primarily, to examine the neural correlates of fear reinstatement using functional magnetic resonance imaging (FMRI). In Experiment 1, human subjects were exposed to differential auditory fear conditioning followed by extinction of the fear response in either the same context in which conditioning occurred or a novel context. Following extinction, all subjects received unsignalled UCS presentations, which served as a reminder of their original training experience, and were then shown a visual background stimulus from either the original training context or the extinction context. Although there were no differences between groups during the acquisition session, behavior significantly differed between groups depending on the context in which a reminder cue was delivered. These findings suggest that autonomic and declarative responses are modulated by contextual cues in humans, and are consistent with research on fear reinstatement in laboratory animals. In Experiment 2, FMRI was used to determine the neural networks involved in fear reinstatement following extinction training. Human subjects were exposed to differential fear conditioning with visual stimuli, and extinction training occurred either in the original training context or in a mock scanner. All subjects underwent fear reinstatement in the original training context. Significant differences were found in the resultant FMRI brain maps during the reinstatement phase, especially in areas known to be involved in fear conditioning, including the amygdala, hippocampus, anterior cingulate, and sensory cortex. The results from Experiment 2 provide evidence that the functional network among medial temporal and frontal regions is modified depending on the emotional significance of environmental cues, thus amplifying or inhibiting fear expression.