Functional specialization in the human medial temporal lobe

Abstract

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

Figure 1.

Three coronal MRI scan slices for one representative patient from the hippocampal (a) and MTL (b) patient groups are shown (arrows highlight regions of significant damage). L, Left; R, right. Reproduced with permission from Lee et al. (2005a).

Figure 2.

Concurrent object discrimination task. Subjects learned 11 discrimination problems, in which the number of objects was held constant, but the degree of feature ambiguity was varied systematically. Each discrimination problem consisted of four objects, presented in pairs. Two of the four objects were designated correct (targets), and two were designated incorrect (nontargets). In each pair, only one object was a target (shown here on the left). The pairs of objects were presented continuously in a pseudorandom order until the subject selected the target objects for eight consecutive trials. Stimuli, Each object consisted of the conjunction of the following two stimulus features: barcode components (a; individual features shown as letters for illustrative purposes) and bug parts (b; body and legs). Shape and fill were the manipulated features for the blobs stimulus set; body plan and coat pattern were used for the beast stimulus set. For examples of these stimuli, see Figure 3. Ambiguity, There were three feature ambiguity conditions: minimum ambiguity, in which no features were explicitly ambiguous (i.e., each feature was consistently either part of a target or a nontarget); intermediate ambiguity, in which one feature in each object (e.g., legs) was ambiguous; and maximum ambiguity, in which all features were ambiguous (i.e., each feature was simultaneously present in a target and nontarget object).

Figure 3.

Mean errors to criterion (8 consecutive correct responses) for the two patient groups and two control groups (averaged) for blobs (a), barcodes (b), bugs (c), and beasts (d) are shown. There was no significant difference between the young and old controls. One MTL patient was unable to achieve the criterion of eight consecutive correct for maximum-ambiguity blobs, intermediate-ambiguity barcodes, and maximum-ambiguity barcodes (>140 trials). Objects used in the maximum-ambiguity condition of each stimulus type are shown on each graph. Correct objects are depicted on the left; incorrect objects are on the right. Error bars represent SEM. ^**p < 0.01 (MTL group vs control).