Equivalent activation of the hippocampus by face-face and face-laugh paired associate learning and recognition.

The human hippocampus is known to play an important role in relational memory. Both patient lesion studies and functional-imaging studies have shown that it is involved in the encoding and retrieval from memory of arbitrary associations. Two recent patient lesion studies, however, have found dissociations between spared and impaired memory within the domain of relational memory. Recognition of associations between information of the same kind (e.g., two faces) was spared, whereas recognition of associations between information of different kinds (e.g., face-name or face-voice associations) was impaired by hippocampal lesions. Thus, recognition of associations between information of the same kind may not be mediated by the hippocampus. Few imaging studies have directly compared activation at encoding and recognition of associations between same and different types of information. Those that have have shown mixed findings and been open to alternative interpretation. We used fMRI to compare hippocampal activation while participants studied and later recognized face-face and face-laugh paired associates. We found no differences in hippocampal activation between our two types of stimulus materials during either study or recognition. Study of both types of paired associate activated the hippocampus bilaterally, but the hippocampus was not activated by either condition during recognition. Our findings suggest that the human hippocampus is normally engaged to a similar extent by study and recognition of associations between information of the same kind and associations between information of different kinds.

Integrating visual and tactile information in the perirhinal cortex.

By virtue of its widespread afferent projections, perirhinal cortex is thought to bind polymodal information into abstract object-level representations. Consistent with this proposal, deficits in cross-modal integration have been reported after perirhinal lesions in nonhuman primates. It is therefore surprising that imaging studies of humans have not observed perirhinal activation during visual-tactile object matching. Critically, however, these studies did not differentiate between congruent and incongruent trials. This is important because successful integration can only occur when polymodal information indicates a single object (congruent) rather than different objects (incongruent). We scanned neurologically intact individuals using functional magnetic resonance imaging (fMRI) while they matched shapes. We found higher perirhinal activation bilaterally for cross-modal (visual-tactile) than unimodal (visual-visual or tactile-tactile) matching, but only when visual and tactile attributes were congruent. Our results demonstrate that the human perirhinal cortex is involved in cross-modal, visual-tactile, integration and, thus, indicate a functional homology between human and monkey perirhinal cortices.

Two case studies illustrating how relatively selective hippocampal lesions in humans can have quite different effects on memory.

Two patients, with magnetic resonance imaging (MRI)-confirmed relatively selective hippocampal damage, showed distinct patterns of performance on tests of recall, item recognition, and associative recognition. Patient AC showed a mean bilateral volume reduction of the hippocampus of 28%, but displayed no memory deficit. Both recall and recognition memory were unimpaired. In contrast, patient PR, who showed a mean bilateral hippocampal volume reduction of 59%, was more consistently impaired on recall than recognition tests, although his recognition scores were highly variable. Patients AC and PR illustrate how variable the memory deficit following seemingly selective hippocampal damage can be in humans. They highlight the need for more sophisticated imaging in future studies if the human hippocampus' role in memory is to be fully identified.

The role of the human medial temporal lobe in object recognition and object discrimination.

This paper reviews evidence from neuropsychological patient studies relevant to two questions concerning the functions of the medial temporal lobe in humans. The first is whether the hippocampus and the adjacent perirhinal cortex make different contributions to memory. Data are discussed from two patients with adult-onset bilateral hippocampal damage who show a sparing of item recognition relative to recall and certain types of associative recognition. It is argued that these data are consistent with Aggleton and Brown's (1999) proposal that familiarity-based recognition memory is not dependent on the hippocampus but is mediated by the perirhinal cortex and dorso-medial thalamic nucleus. The second question is whether the recognition memory deficit observed in medial temporal lobe amnesia can be explained by a deficit in perceptual processing and representation of objects rather than a deficit in memory per se. The finding that amnesics were impaired at recognizing, after short delays, patterns that they could successfully discriminate suggests that their memory impairment did not result from an object-processing deficit. The possibility remains, however, that the human perirhinal cortex plays a role in object processing, as well as in recognition memory, and data are presented that support this possibility.

Item recognition is less impaired than recall and associative recognition in a patient with selective hippocampal damage.

This article explores the recall, item recognition, and associative recognition memory of patient B.E., whose pattern of retrograde amnesia was reported by Kapur and Brooks (1999; Hippocampus 9:1-8). Structural magnetic resonance imaging (MRI) has shown that B.E. has bilateral damage restricted to the hippocampus. The structural damage he had sustained was accompanied by bilateral hypoperfusion of the temporal lobe, revealed by positron emission tomography (PET), and which single photon emission computed tomography (SPECT) suggested was greater in the left than the right temporal lobe. B.E. showed a global anterograde amnesia for verbal material, but he displayed some sparing of nonverbal item recognition relative to nonverbal recall and associative recognition. His performance on an item recognition task that used the remember/know procedure and another that involved repetition of the test phase, to reduce the difference between the familiarity of the targets and foils, suggested that his relatively spared nonverbal item recognition may have been mainly supported by familiarity. This finding is consistent with the view that the anterior temporal lobe, including the perirhinal cortex, can support familiarity-based memory judgments (Brown and Bashir, 2002; Philos Trans R Soc Lond B 357:1083-1095). B.E.'s data also highlight the importance of functional as well as structural scan information for interpreting the pattern of memory deficits shown by patients with selective hippocampal structural lesions.

Associative recognition in a patient with selective hippocampal lesions and relatively normal item recognition.

Previous work (Mayes et al., Hippocampus 12:325-340, 2002) found that patient YR, who suffered a selective bilateral lesion to the hippocampus in 1986, showed relatively preserved verbal and visual item recognition memory in the face of clearly impaired verbal and visual recall. In this study, we found that YR's Yes/No as well as forced-choice recognition of both intra-item associations and associations between items of the same kind was as well preserved as her item recognition memory. In contrast, YR was clearly impaired, and more so than she was on the above kinds of recognition, at recognition of associations between different kinds of information. Thus, her recognition memory for associations between objects and their locations, words and their temporal positions, abstract visual items or words and their temporal order, animal pictures and names of professions, faces and voices, faces and spoken names, words and definitions, and pictures and sounds, was clearly impaired. Several of the different information associative recognition tests at which YR was impaired could be compared with related item or inter-item association recognition tests of similar difficulty that she performed relatively normally around the same time. It is suggested that YR's familiarity memory for items, intra-item associations, and associations between items of the same kind was mediated by her intact medial temporal lobe cortices and was preserved, whereas her hippocampally mediated recall/recollection of these kinds of information was impaired. It is also suggested that the components of associations between different kinds of information are represented in distinct neocortical regions and that initially they only converge for memory processing within the hippocampus. No familiarity memory may exist in normal subjects for such associations, and, if so, YR's often chance recognition occurred because of her severe recall/recollection deficit. Conflicting data and views are discussed, and the way in which recall as well as item and associative recognition need to be systematically explored in patients with apparently selective hippocampal lesions, in order to resolve existing conflicts, is outlined.

Visual paired comparison performance is impaired in a patient with selective hippocampal lesions and relatively intact item recognition.

In this study, we have examined visual recognition memory in a patient, YR, with discrete hippocampal damage who has shown normal or nearly normal item recognition over a large number of tests. We directly compared her performance as measured using a visual paired comparison task (VPC) with her performance on delayed matching to sample (DMS) tasks. We also investigated the effect of retention interval between familiarisation and test. YR shows good visual recognition with the DMS task up to 10 s after the familiarisation period, but only shows recognition with the VPC task for the shortest retention interval (0 s). Our results are consistent with the view that hippocampal damage disrupts recollection and recall, but not item familiarity memory.

Relative sparing of item recognition memory in a patient with adult-onset damage limited to the hippocampus.

There is disagreement about whether selective hippocampal lesions in humans cause clear item recognition as well as recall deficits. Whereas Reed and Squire (Behav Neurosci 1997;111:667-775) found that patients with adult-onset relatively selective hippocampal lesions showed clear item recognition deficits, Vargha-Khadem et al. (Science 1997;277: 376-380, Soc Neurosci Abstr 1998;24:1523) found that 3 patients who suffered selective hippocampal damage in early childhood showed clear recall deficits, but had relatively normal item recognition. Manns and Squire (Hippocampus 1999;9:495-499) argued, however, that item recognition may have been spared in these patients because the early onset of their pathology allowed compensatory mechanisms to develop. Therefore, to determine whether early lesion onset is critical for the relative sparing of item recognition and to determine whether its occurrence is influenced by task factors, we extensively examined item recognition in patient Y.R., who has pathology of adult-onset restricted to the hippocampus. Like the developmental cases, she showed clear free recall deficits on 34 tests, but her item recognition on 43 tests was relatively spared, and markedly less disrupted than her recall. Her item recognition performance relative to that of her controls was not significantly influenced by whether tests tapped visual or verbal materials, had a yes/no or forced-choice format, contained few or many items, had one or several foils per target item, used short or very long delays, or were difficult or easy for normal subjects. Interestingly, YR's bilateral hippocampal destruction was greater than at least 2 of the 3 patients of Manns and Squire (Hippocampus 1999;9:495-499). The possible reasons why item recognition differs across patients with relatively selective hippocampal damage of adult-onset and how the reasons that are truly critical can be best identified are discussed.

Under what conditions is recognition spared relative to recall after selective hippocampal damage in humans?

The claim that recognition memory is spared relative to recall after focal hippocampal damage has been disputed in the literature. We examined this claim by investigating object and object-location recall and recognition memory in a patient, YR, who has adult-onset selective hippocampal damage. Our aim was to identify the conditions under which recognition was spared relative to recall in this patient. She showed unimpaired forced-choice object recognition but clearly impaired recall, even when her control subjects found the object recognition task to be numerically harder than the object recall task. However, on two other recognition tests, YR's performance was not relatively spared. First, she was clearly impaired at an equivalently difficult yes/no object recognition task, but only when targets and foils were very similar. Second, YR was clearly impaired at forced-choice recognition of object-location associations. This impairment was also unrelated to difficulty because this task was no more difficult than the forced-choice object recognition task for control subjects. The clear impairment of yes/no, but not of forced-choice, object recognition after focal hippocampal damage, when targets and foils are very similar, is predicted by the neural network-based Complementary Learning Systems model of recognition. This model postulates that recognition is mediated by hippocampally dependent recollection and cortically dependent familiarity; thus hippocampal damage should not impair item familiarity. The model postulates that familiarity is ineffective when very similar targets and foils are shown one at a time and subjects have to identify which items are old (yes/no recognition). In contrast, familiarity is effective in discriminating which of similar targets and foils, seen together, is old (forced-choice recognition). Independent evidence from the remember/know procedure also indicates that YR's familiarity is normal. The Complementary Learning Systems model can also accommodate the clear impairment of forced-choice object-location recognition memory if it incorporates the view that the most complete convergence of spatial and object information, represented in different cortical regions, occurs in the hippocampus.

Differential involvement of the hippocampus and temporal lobe cortices in rapid and slow learning of new semantic information.

The present study examined the rapid and slow acquisition of new semantic information by two patients with differing brain pathology. A partial double dissociation was found between the patterns of new learning shown by these two patients. Rapid acquisition was impaired in a patient (YR) who had relatively selective hippocampal damage, but it was unimpaired in another patient (JL) who, according to structural MRI, had an intact hippocampus but damage to anterolateral temporal cortex accompanied by epileptic seizures. Slow acquisition was impaired in both patients, but was impaired to a much greater extent in JL. The dissociation suggests that the mechanisms underlying rapid and slow acquisition of new semantic information are at least partially separable. The findings indicate that rapid acquisition of semantic, as well as episodic information, is critically dependent on the hippocampus. However, they suggest that hippocampal processing is less important for the gradual acquisition of semantic information through repeated exposure, although it is probably necessary for normal levels of such learning to be achieved.

Memory for single items, word pairs, and temporal order of different kinds in a patient with selective hippocampal lesions.

One kind of between-list and two kinds of within-list temporal order memory were examined in a patient with selective bilateral hippocampal lesions. This damage disrupted memory for all three kinds of temporal order memory, but left item and word pair recognition relatively intact. These findings are inconsistent with claims that (1) hippocampal lesions, like those of the medial temporal lobe (MTL) cortex, disrupt item and word pair recognition, and that (2) hippocampal lesions disrupt temporal order memory and item recognition to the same degree. Not only was word pair recognition intact in the patient, but further evidence indicates that her recognition of other associations between items of the same kind is also spared so retrieval of such associations cannot be sufficient to support within-list temporal order recognition. Rather, as other evidence indicates that the patient is impaired at recognition of associations between different kinds of information, within-list (and possibly between-list) temporal order memory may be impaired by hippocampal lesions because it critically depends on retrieving associations between different kinds of information.

Perceptual and mnemonic matching-to-sample in humans: contributions of the hippocampus, perirhinal and other medial temporal lobe cortices.

Two questions were addressed by the present study. The first was whether the previously reported item recognition deficit which is shown by amnesic patients may be due to a perceptual rather than a memory deficit. To address this question a group of amnesic patients were tested on a 14-choice forced-choice visual item recognition test which included a "simultaneous" condition in which the sample remained visible during the matching decision and a zero second delay. Eacott, Gaffan and Murray (1994) have reported an impairment in simultaneous matching-to-sample following perirhinal damage in monkeys. In our amnesic patients, a deficit was found only after filled delays of 10 seconds or longer and this was also the case for a subgroup of patients whose damage included the perirhinal cortex. The second question, which arose from the model of Aggleton and Brown (1999), was whether performance on the DMS task would remain intact following selective damage to the hippocampus. We tested a patient with bilateral damage to the hippocampus on the 14-choice DMS task and found that her performance was not significantly impaired at delays of up to 30 seconds.

Factor analysis of three standardized tests of memory in a clinical population.

OBJECTIVES: The aim of this study was to determine the factor structure of three standardized memory tests: Wechsler Memory Scale-Revised (WMS-R), Warrington Recognition Memory Test (WRMT), Doors and People Test (D&P). We investigated whether these different standardized tests of memory are consistent in their evaluation of memory function, and the extent to which these tests discriminate between different memory functions (e.g. recall/recognition and verbal/non-verbal memory). DESIGN: Fifty patients with selective memory impairment were tested on the WMS-R, WRMT and D&P. METHODS: Age-scaled scores from selective measures of these tests (WMS-R-verbal, WMS-R-visual, WMS-R-delay, WRMT-words, WRMT-faces, D&P-people, D&P-doors, D&P-shapes, D&P-names) were used as input to a factor analysis. RESULTS: Maximum likelihood factor analysis yielded a three-factor solution consistent with a theoretically motivated fractionation of memory function into recall and recognition components. Recognition performance, but not recall performance, showed dissociation into visual and verbal components. CONCLUSIONS: The WMS-R, WRMT and D&P are highly consistent in their assessment of memory function. The results of the factor analysis are consistent with a theoretically motivated fractionation of recall and recognition memory. They are also partially consistent with a dissociation between visual and verbal memory function.

A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage.

The spatial memory of a single patient (YR) was investigated. This patient, who had relatively selective bilateral hippocampal damage, showed the pattern of impaired recall but preserved item recognition on standardised memory tests that has been suggested by Aggleton and Shaw [Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis of psychometric data. Neuropsychologia 1996;34:51-62] to be a consequence of Papez circuit lesions. YR was tested on three recall tests and one recognition test for visuospatial information. The initial recall test assessed visuospatial memory over very short unfilled delays and YR was not significantly impaired. This test was then modified to test recall of allocentric and egocentric spatial information separately after filled delays of between 5 and 60 s. YR was found to be more impaired at recalling allocentric than egocentric information after a 60 s interval with a tendency for the impairment to increase up to this delay. Recognition of allocentric spatial information was also assessed after delays of 5 and 60 s. YR was impaired after the 60 s delay. The results suggest that the human hippocampus has a greater involvement in allocentric than egocentric spatial memory, and that this most likely concerns the consolidation of allocentric information into long-term memory rather than the initial encoding of allocentric spatial information. The findings also suggest that YR's item recognition/free recall deficit pattern reflects a problem retrieving or storing certain kinds of associative information.

A comparison of egocentric and allocentric spatial memory in medial temporal lobe and Korsakoff amnesics.

Two patients with medial temporal lobe damage, seven Korsakoff amnesics and fourteen healthy control subjects were tested on three conditions of a spatial memory test ('short delay', 'allocentric' and 'egocentric'). The task required subjects to recall the position of a single spot of light presented on a board after various delays. The 'short delay' condition tested memory over very short, unfilled intervals. The other two conditions used longer, filled delays. The allocentric condition required subjects to move to a different place around the board before recalling the position of the light. In the egocentric condition stimuli were presented in darkness, which eliminated allocentric cues. The Korsakoff amnesics were impaired at all delays of the short delay tasks, suggesting poor encoding. On the allocentric and egocentric tasks the Korsakoff amnesics showed a comparable impairment in the two conditions, which worsened with delay. This accelerated forgetting suggested that the Korsakoff amnesics also had impaired memory for allocentric and egocentric information. The patients with medial temporal lobe damage were unimpaired in the 'short delay' condition suggesting intact encoding and short-term memory of spatial information. However, they were impaired in the allocentric condition and showed accelerated loss of allocentric spatial information. In the egocentric condition, while the performance of one patient was impaired, the performance of the other was as good as controls. This result suggests that, in contrast to allocentric spatial memory, which is sensitive to medial temporal lobe damage, an intact medial temporal lobe need not be necessary for successful performance on an egocentric spatial memory task.

Do amnesics forget colours pathologically fast?

We tested amnesic and control subjects on a task which required the recognition of single, difficult to name colours, after delays ranging from 7 seconds to 120 seconds after performance of the two subject groups had been matched at the shortest delay by giving the amnesic patients longer study time. The amnesic patients showed abnormally fast forgetting over the two minute period. Furthermore, a subgroup of nine subjects with presumed damage to midline diencephalic structures (Korsakoff's syndrome) were found to forget as fast as a group of six subjects with presumed medial temporal lobe damage (herpes simplex encephalitis). These results contrast both with studies using the Huppert and Piercy procedure and those using the Brown-Peterson task, none of which have shown convincing evidence of accelerated forgetting in medial temporal lobe or diencephalic amnesia.

The performance of amnesic subjects on tests of delayed matching-to-sample and delayed matching-to-position.

Forced-choice tests of recognition have become the favoured behavioural method for the assessment of models of amnesia in nonhuman primates, yet the profile of deficits shown by human amnesic subjects remains uncertain. The present study explored the performance of 12 amnesic subjects on two delayed matching-to-sample tasks. Experiment 1, which used retention delays of between 2 and 60 sec, confirmed that amnesia impairs such tasks, even when there is only one item to be remembered. The results also highlighted the need to match levels of performance before the effects of delay can be interpreted. In Experiment 2 care was taken to eliminate ceiling effects and to match the subjects at the shortest delay (3 sec). This was achieved by giving the control subjects harder versions of the same task. The amnesic subjects still showed a faster rate of forgetting for abstract patterns, indicating that this is a genuine feature of amnesia. In contrast, the amnesic subjects' performance on a spatial matching-to-sample task was not differentially affected by delays of up to 40 sec. There was no evidence that the amnesic subjects were disproportionately impaired on this spatial task, nor could the different aetiological groups be distinguished by their patterns of DMS performance.

Modulation of event-related brain potentials by word repetition: effects of local context.

In four experiments, event-related brain potentials (ERPs) were evoked by visually presented word pairs in a task requiring responses to occasional target pairs. In Experiments 1 and 2, some pairs comprised items that had been presented previously. These repeated pairs consisted of words that had been paired together when first presented (same context condition) or words that had first been presented on consecutive trials (different context condition). ERP repetition effects were equivalent in the two conditions. In Experiment 3, same-context repeats were contrasted with a condition in which a repeated word was paired with a new word. Only the same-context pairs evoked a repetition effect. Experiment 4 showed that repetition effects to different- and same-context repeats remained equivalent when first presentations of the members of different-context pairs were separated by six intervening trials. We conclude that the ERP repetition effect shows little sensitivity to local context.

Word repetition effects on event-related potentials in healthy young and old subjects, and in patients with Alzheimer-type dementia.

Event-related potentials (ERPs) were recorded from 16 healthy young (mean age 21 years) and 16 healthy old subjects (mean age 64 years), and from 11 subjects with a diagnosis of Dementia of Alzheimer Type (DAT). The task requirement was to attend to a series of visually presented words so as to respond to occasional animal names. Non-animal names repeated after either a single or six intervening items. In the young subjects ERPs evoked by repeated words displayed a widespread, sustained positive-going shift relative to ERPs evoked by first presentations (the ERP repetition effect). This effect onset around 220 msec and did not differ as a function of inter-item lag. Other than for a delay in onset of approximately 80 msec, the ERP repetition effect in the healthy old group was in all respects equivalent to that of the young subjects. The ERP repetition effects in the DAT patients were statistically indistinguishable from those of an appropriately matched sub-set of the healthy old subjects. These results indicate that the ERP repetition effect remains robust in subjects in whom explicit memory has declined as a result of normal aging or DAT. Thus they suggest that the effect reflects processes independent of those underlying explicit memory, and that it may index a form of memory relatively unaffected by the pathology underlying DAT.