Associative learning is thought to depend on detecting mismatches between actual and expected experiences. With functional magnetic resonance imaging (FMRI), we studied brain activity during different types of mismatch in a paradigm where contrastingcolored lights signaled the delivery of painful heat, nonpainful warmth, or no stimulation. When painful heat stimulation was unexpected, there was increased FMRI signal intensity in areas of the hippocampus, superior frontal gyrus, cerebellum, and superior parietal gyrus that was not found with mismatch between expectation and delivery of nonpainful warmth stimulation. When painful heat stimulation was unexpectedly omitted, the FMRI signal intensity decreased in the left superior parietal gyrus and increased in the other regions. These contrasting activation patterns correspond to two different mismatch concepts in theories of associative learning (Rescorla-Wagner, temporal difference vs. Pearce-Hall, Mackintosh). Searching for interventions to specifically modulate activation of these brain regions therefore offers an approach to identifying new treatments for chronic pain, which often has a substantial associative learning component.L earning cues of impending pain allows future painful events to be anticipated and avoided (1, 2). Thus, learning associations between pain and predictive cues has fundamental adaptive value. However, such learning also can have adverse effects. It can exacerbate the unpleasantness of pain (3, 4) and can contribute to chronic pain states (5). We previously have identified brain regions activated by cues associated with pain (6). In this paper, we isolate brain regions that play a critical role in learning cue-pain associations.Learning of a cue-outcome association only takes place when there is a mismatch between outcome and the expectations based on perceived cues (7,8). The first goal of the present study, therefore, was to identify brain regions whose activation pattern is consistent with detecting mismatches between the expectation and the delivery of painful stimulation.The related second goal was to study the extent to which this mismatch-related brain activity conforms to predictions derived from theories of Pavlovian conditioning (9-12), which have formalized the relationship between mismatch detection and associative learning. In these models, mismatch is represented as the difference Ϫ V. Applied to associative learning about pain, represents the intensity of the actual pain and V represents the accumulated strength of the cue-pain association (i.e., the expectation of pain based on the cue). Associative learning corresponds to changes in V. When the intensity of a painful stimulus exceeds expectation, V is increased proportionally to the magnitude of the mismatch. The rate of learning decelerates over successive learning trials as V approaches .What happens, however, when the expectation exceeds the actual pain? In this situation, different models of associative learning have distinct predictions. In one theory (9), mismatc...

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In two experiments the involvement of the nucleus accumbens in instrumental conditioning was investigated using rats as subjects. In experiment 1, extensive bilateral cytotoxic lesions of the nucleus accumbens mildly suppressed instrumental responding reinforced with food, but had no detectable effect on the sensitivity of the rats' performance either to outcome devaluation or to degradation of the instrumental contingency. In experiment 2, restricted accumbens lesions reliably attenuated the excitatory effect of systemically administered d-amphetamine on lever pressing for a conditioned reinforcer, and completely abolished Pavlovian-instrumental transfer. Taken together these results give a picture of the involvement of the rat nucleus accumbens in instrumental conditioning. They support the widely held theory that the nucleus accumbens mediates the excitatory effects of appetitively conditioned Pavlovian signals on instrumental performance and refute the hypothesis that the nucleus accumbens is part of the neural circuitry by which incentive value is attached to the representations of instrumental outcomes.