Previous functional magnetic resonance imaging (fMRI) studies with human subjects have explored the neural substrates involved in forming associations in Pavlovian fear conditioning. Most of these studies used delay procedures, in which the conditioned stimulus (CS) and unconditioned stimulus (UCS) coterminate. Less is known about brain regions that support trace conditioning, a procedure in which an interval of time (trace interval) elapses between CS termination and UCS onset. Previous work suggests significant overlap in the neural circuitry supporting delay and trace fear conditioning, although trace conditioning requires recruitment of additional brain regions. In the present event-related fMRI study, skin conductance and continuous measures of UCS expectancy were recorded concurrently with whole-brain blood oxygenation level-dependent (BOLD) imaging during direct comparison of delay and trace discrimination learning. Significant activation was observed within the visual cortex for all CSs. Anterior cingulate and medial thalamic activity reflected associative learning common to both delay and trace procedures. Activations within the supplementary motor area (SMA), frontal operculum, middle frontal gyri, and inferior parietal lobule were specifically associated with trace interval processing. The hippocampus displayed BOLD signal increases early in training during all conditions; however, differences were observed in hippocampal response magnitude related to the accuracy of predicting UCS presentations. These results demonstrate overlapping patterns of activation within the anterior cingulate, medial thalamus, and visual cortex during delay and trace procedures, with additional recruitment of the hippocampus, SMA, frontal operculum, middle frontal gyrus, and inferior parietal lobule during trace conditioning. These data suggest that the hippocampus codes temporal information during trace conditioning, whereas brain regions supporting working memory processes maintain the CS-UCS representation during the trace interval.

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Although laboratory animal studies have shown that the amygdala plays multiple roles in conditional fear, less is known about the human amygdala. Human subjects were trained in a Pavlovian fear conditioning paradigm during functional magnetic resonance imaging (fMRI). Brain activity maps correlated with reference waveforms representing the temporal pattern of visual conditional stimuli (CSs) and subject-derived autonomic responses were compared. Subjects receiving paired CS-shock presentations showed greater amygdala activity than subjects receiving unpaired CS-shock presentations when their brain activity was correlated with a waveform generated from their behavioral responses. Stimulusbased waveforms revealed learning differences in the visual cortex, but not in the amygdala. These data support the view that the amygdala is important for the expression of learned behavioral responses during Pavlovian fear conditioning.

We asked what kind of memory is operating when eye movements change as the result of experience. Participants viewed scenes that were either novel, repeated, or manipulated (i.e., a change was introduced in one region of the scene). Eye movements differed depending on the past viewing history of each scene. Participants made fewer fixations and sampled fewer regions when scenes were repeated than when scenes were novel. When scenes were altered, participants made more fixations in the altered region, spent more time looking at the altered region, and made more transitions into and out of the altered region than in unchanged (matched) regions in the repeated scenes. Importantly, these effects occurred only when individuals were aware that a change had occurred. Participants who were unaware that the scene had been altered looked at the changed scenes in the same way that they looked at repeated scenes. Thus, there was no indication that eye movements could reveal an unaware (unconscious) form of memory. Instead, eye movements reflected conscious memory of whether the scene was repeated or manipulated. The findings were the same when awareness was assessed after viewing all the scenes (experiment 1) and when awareness was assessed after each scene was presented (experiment 2). In experiment 3, memory-impaired patients with damage limited to the hippocampus were impaired at deciding whether scenes were novel, repeated, or manipulated. Thus, the ability to consciously recollect recent encounters with scenes reflects a form of hippocampus-dependent memory. The findings show that experience-dependent eye movements in response to altered scenes reflect conscious, declarative memory, and they support the link between aware memory, declarative memory, and hippocampus-dependent memory.