Perirhinal cortex and area TE are immediately adjacent to each other in the temporal lobe and reciprocally interconnected. These areas are thought to lie at the interface between visual perception and visual memory, but it has been unclear what their separate contributions might be. In three experiments, monkeys with bilateral lesions of the perirhinal cortex exhibited a different pattern of impairment than monkeys with bilateral lesions of area TE. In experiment 1, lesions of the perirhinal cortex produced a multimodal deficit in recognition memory (delayed nonmatching to sample), whereas lesions of area TE impaired performance only in the visual modality. In experiment 2, on a test of visual recognition memory (the visual paired comparison task) lesions of the perirhinal cortex impaired performance at long delays but spared performance at a very short delay. In contrast, lesions of area TE impaired performance even at the short delay. In experiment 3, lesions of the perirhinal cortex and lesions of area TE produced an opposite pattern of impairment on two visual discrimination tasks, simple object discrimination learning (impaired only by perirhinal lesions), and concurrent discrimination learning (impaired only by TE lesions). Taken together, the findings suggest that the perirhinal cortex, like other medial temporal lobe structures, is important for the formation of memory, whereas area TE is important for visual perceptual processing.

The present study investigates whether the ability to classify on the basis of rules can be learned independently of memory for the specific instances used to leach the rules. Thirteen amnesic patients and 14 control subjects studied letter strings generated by an artificial grammar. Subjects were then shown new letter strings and were instructed to classify them as grammatical or nongrammatical. Amnesic patients performed as well as normal subjects. However, amnesic patients performed more poorly than control subjects on a recognition test of the exemplars that had been presented. Amnesic patients also performed more poorly than control subjects when the instructions were to base the classification on explicit comparison with the original exemplars. The results show that classification learning based on exemplars of an artificial grammar can develop normally despite impaired memory for the exemplars themselves. Whereas exemplar memory depends on interactions between neocortex and the limbic system, classification learning may depend on interaction between neocortex and the neostriatum.

Addictive drugs, such as cocaine, cause long-lasting neural changes in prefrontal cortex. It has been hypothesized that these changes affect the behavioural control mediated by orbitofrontal cortex. To test this hypothesis, rats were given injections of cocaine (30 mg/kg/d, i.p.) or vehicle for 14 days and then trained after a 2-week withdrawal period in an odor discrimination task sensitive to the effects of orbitofrontal cortex lesions. We found that cocaine-treated rats, who demonstrated long-lasting sensitization to the locomotor activating effects of cocaine, failed to show normal changes in response latency during discrimination learning and were also slower than controls to acquire serial reversals. These behavioural impairments are identical to the effects of orbitofrontal cortex lesions in this task and show that cocaine exposure in rats can cause long-lasting effects on orbitofrontal-dependent functions. Notably, these effects were not correlated with increases in locomotor activity linked to cocaine-induced psychomotor sensitization observed before or after training, suggesting that the brain changes underlying the behavioural effects in the discrimination task are different from those mediating psychomotor sensitization.

During the past decade, work with monkeys has helped identify the structures in the medial temporal lobe that are important for memory: the hippocampal region (including the hippocampus proper, the dentate gyrus, and the subicular complex) and adjacent cortical areas that are anatomically linked to the hippocampus, i.e., the entorhinal, perirhinal, and parahippocampal cortices. One idea that has emerged from this work is that the severity of memory impairment might increase as more components of the medial temporal lobe are damaged. We have evaluated this idea directly by examining behavioral data from 30 monkeys (ten normal monkeys and 20 monkeys with bilateral lesions involving structures within the medial temporal lobe) that have completed testing on our standard memory battery during the last 10 years. The main finding was that the severity of memory impairment depended on the locus and extent of damage to the medial temporal lobe. Specifically, damage limited to the hippocampal region produced a mild memory impairment. More severe memory impairment was produced when the damage was increased to include the adjacent entorhinal and parahippocampal cortices (the H+ lesion). Finally, memory impairment was even more severe when the H+ lesion was extended forward to include the anterior entorhinal cortex and the perirhinal cortex (H++ lesion). Taken together, these findings suggest that, whereas damage to the hippocampal region produces measurable memory impairment, a substantial part of the severe memory impairment produced by large medial temporal lobe lesions in humans and monkeys can be attributed to damage to entorhinal, perirhinal, and parahippocampal cortices adjacent to the hippocampal region.

The orbitofrontal cortex (OF) is strongly and reciprocally connected with the perirhinal (PR) and entorhinal areas of the medial temporal lobe and plays an important role in odor recognition memory. This study characterized firing patterns of single neurons in the OF of rats performing a continuous odor-guided delayed nonmatch to sample (DNMS) task. Most OF neurons fired in association with one or more task events, including the initiation of trials, the sampling of odor stimuli, and the consumption of rewards. OF neurons also exhibited sustained odorselective activity during the memory delay, and a large proportion of OF cells had odor-specific enhanced or suppressed responses on stimulus repetition. Most OF neurons were activated during several task events, or associated with complex behavioral states. The incidence of cells that fired in association with the critical match/non-match judgement was increased as the DNMS rule was learned, and was higher in OF than in perirhinal and entorhinal cortex. Furthermore, the classification of match and nonmatch trials was correlated with accuracy in performance of that judgement. These findings are consistent with the view that OF is a high order association cortex that plays a role both in the memory representations for specific stimuli and in the acquisition and application of task rules.