The human perirhinal cortex and recognition memory

The importance of the perirhinal cortex for visual recognition memory performance is undisputed. However, it has not been clear whether its contribution to performance is mainly perceptual, or mainly mnemonic, or whether the perirhinal cortex contributes to both perception and memory. We determined the effects of medial temporal lobe damage that includes complete damage to the perirhinal cortex in two amnesic patients by assessing recognition memory for complex visual stimuli across delays from 0 to 40 s. These patients, as well as six other amnesic patients with damage limited to the hippocampal formation or diencephalic structures, exhibited intact recognition memory at delays of 0–2 s and a delay-dependent memory impairment at delays of 6 s and longer. Additionally, the patients with damage to the perirhinal cortex performed worse than the other amnesic patients at delays of 25 s and longer. The findings suggest that the perirhinal cortex is not important for visual perception or immediate memory. In this respect, the findings for perirhinal cortex resemble the findings for other medial temporal lobe structures, including the hippocampus. Hippocampus 1998;8:330–339. © 1998 Wiley-Liss, Inc.     

It does not look odd to me: Perceptual impairments and eye movements in amnesic patients with medial temporal lobe damage

Studies of people with memory impairments have shown that a specific set of brain structures in the medial temporal lobe (MTL) is vital for memory function. However, whether these structures have a role outside of memory remains contentious. Recent studies of amnesic patients with damage to two structures within the MTL, the hippocampus and the perirhinal cortex, indicated that these patients also performed poorly on perceptual tasks. More specifically, they performed worse than controls when discriminating between objects, faces and scenes with overlapping features. In order to investigate whether these perceptual deficits are reflected in their viewing strategies, we tested a group of amnesic patients with MTL damage that included the hippocampus and perirhinal cortex on a series of oddity discrimination tasks in which they had to select an odd item from a visual array. Participants' eye movements were monitored throughout the experiment. Results revealed that patients were impaired on tasks that required them to discriminate between items that shared many features, and tasks that required processing items from different viewpoints. An analysis of their eye movements revealed that they exhibited a similar viewing pattern as controls: they fixated more on the target item on trials answered correctly, but not on trials answered incorrectly. In addition, their impaired performance was not explained by an abnormal viewing-strategy that assessed their use of working memory. These results suggest that the perceptual deficits in the MTL patients are not a consequence of abnormal viewing patterns of the objects and scenes, but instead, could involve an inability to bind information gathered from several fixations into a cohesive percept. These data also support the view that MTL structures are important not only for long-term memory, but are also involved in perceptual tasks.     

Specialization in the medial temporal lobe for processing of objects and scenes

There has been considerable debate as to whether the hippocampus and perirhinal cortex may subserve both memory and perception. We administered a series of oddity tasks, in which subjects selected the odd stimulus from a visual array, to amnesic patients with either selective hippocampal damage (HC group) or more extensive medial temporal damage, including the perirhinal cortex (MTL group). All patients performed normally when the stimuli could be discriminated using simple visual features, even if faces or complex virtual reality scenes were presented. Both patient groups were, however, severely impaired at scene discrimination when a significant demand was placed on processing spatial information across viewpoint independent representations, while only the MTL group showed a significant deficit in oddity judgments of faces and objects when object viewpoint independent perception was emphasized. These observations provide compelling evidence that the human hippocampus and perirhinal cortex are critical to processes beyond long-term declarative memory and may subserve spatial and object perception, respectively.     

Findings from animals concerning when interactions between perirhinal cortex, hippocampus and medial prefrontal cortex are necessary for recognition memory

Loss of recognition memory is a prominent feature of the human classical amnesic syndrome. Recognition memory requires judgments concerning prior occurrence. Such judgments can be made in a variety of ways using different types of information such as the relative familiarity of individual objects or locations, or the location of a previously encountered object, or when an object was previously encountered. We review findings of selective ablation studies which demonstrate that the perirhinal cortex, hippocampus and medial prefrontal cortex are differently involved in recognition memory processes involving these different types of information. This review also presents data from a series of disconnection analyses, which test whether the perirhinal cortex, hippocampus and medial prefrontal cortex form components of an integrated system for these recognition memory processes. These analyses reveal that it is necessary for the perirhinal cortex, medial prefrontal cortex and the hippocampus to interact, forming an integrated network, in recognition memory involving judgment of whether an object has been previously encountered in a particular place (object-in-place recognition memory) and in judging which of two objects was encountered longer ago (temporal order memory). In contrast, such interactions are not necessary when judgments are made concerning the prior occurrence of an individual item without positional information being necessary for the judgment (object memory) or concerning the prior occurrence of some item at a particular location without object information being necessary for the judgment (location memory).     

The human medial temporal lobe processes online representations of complex objects

There has been considerable debate as to whether structures in the medial temporal lobe (MTL) support both memory and perception, in particular whether the perirhinal cortex may be involved in the perceptual discrimination of complex objects with a large number of overlapping features. Similar experiments testing the discrimination of blended images have obtained contradictory findings, and it remains possible that reported deficits in object perception are due to subtle learning in controls, but not patients. To address this issue, a series of trial-unique object "oddity" tasks, in which subjects selected the odd stimulus from a visual array, were administered to amnesic patients with either selective bilateral damage to the hippocampus or more extensive damage to MTL regions, including the perirhinal cortex. Whereas patients with damage limited to the hippocampus performed similarly to controls on all conditions, patients with perirhinal damage were significantly impaired when the task required discrimination between objects with a large number of features in common. By contrast, when the same stimuli could be discriminated using simple visual features, patients with perirhinal damage performed normally. These results are consistent with a theoretical view which holds that rostral inferotemporal cortical regions, including perirhinal cortex, represent the complex conjunctions of stimulus features necessary for both perception and memory of objects.     

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.     

Recognition memory for faces and scenes in amnesia: dissociable roles of medial temporal lobe structures

The relative contributions of the hippocampus and the perirhinal cortex to recognition memory are currently the subject of intense debate. Whereas some authors propose that both structures play a similar role in recognition memory, others suggest that the hippocampus might mediate recollective and/or associative aspects of recognition memory, whereas the perirhinal cortex may mediate item memory. Here we investigate an alternative functional demarcation between these structures, following reports of stimulus-specific perceptual deficits in amnesics with medial temporal lobe (MTL) lesions. Using a novel recognition memory test for faces and scenes, participants with broad damage to MTL structures, which included the hippocampus and the perirhinal cortex, were impaired on both face and scene memory. By contrast, participants with damage limited to the hippocampus showed deficits only in memory for scenes. These findings imply that although both the hippocampus and surrounding cortex contribute to recognition memory, their respective roles can be distinguished according to the type of material to be remembered. This interaction between lesion site and stimulus category may explain some of the inconsistencies present in the literature.     

Opposite relationship of hippocampal and rhinal cortex damage to delayed nonmatching-to-sample deficits in monkeys

Three recent studies in macaque monkeys that examined the effects on memory of restricted hippocampal lesions (Murray and Mishkin, J Neurosci 1998;18:6568-6582; Beason-Held et al., Hippocampus 1999;9:562-574; Zola et al., J Neurosci 2000;20:451-463) differed in their conclusions about the involvement of the hippocampus in recognition memory. Because these experiments used a common behavioral procedure, trial-unique visual delayed nonmatching-to-sample (DNMS), a quantitative synthesis ("meta-analysis") was performed to determine whether hippocampal lesions produced a reliable net impairment in DNMS performance, and whether this impairment was related to the magnitude of hippocampal damage. A similar analysis was performed on data from monkeys with perirhinal or rhinal cortex damage (Meunier et al., J Neurosci 1993;13:5418-5432; Buffalo et al., Learn Mem 1999;6:572-599). DNMS performance scores were transformed to d' values to permit comparisons across studies, and a loss in d' score, a measure of the magnitude of the recognition deficit relative to the control group, was calculated for each operated monkey. Two main findings emerged. First, the loss in d' following hippocampal damage was reliably larger than zero, but was smaller than that found after lesions limited to the perirhinal cortex. Second, the correlation of loss in d' with extent of hippocampal damage was large and negative, indicating that greater impairments were associated with smaller hippocampal lesions. This relationship was opposite to that between loss in d' and rhinal cortex damage, for which larger lesions were associated with greater impairment. These findings indicate that damage to the hippocampus and to the rhinal cortex affects recognition memory in different ways. Furthermore, they provide a framework for understanding the seemingly disparate effects of hippocampal damage on recognition memory in monkeys, and by extension, for interpreting the conflicting reports on the effects of such damage on recognition memory abilities in amnesic humans.     

Equivalent forgetting rates in long-term memory for diencephalic and medial temporal lobe amnesia.

Amnesia can result from damage to either the midline diencephalon or the medial temporal lobe. An important related question has been whether these two forms of amnesia result in similar or different kinds of memory impairment. Earlier studies raised the possibility that differences might exist in the rate of forgetting within long-term memory, specifically, that the forgetting rate is normal in diencephalic amnesia but abnormally rapid in medial temporal lobe amnesia. In the present study, forgetting was studied in five amnesic patients with damage to the medial temporal lobe, six amnesic patients with damage to the diencephalon, and 10 normal subjects. One hundred twenty pictures were presented to the control subjects for 1 sec each and to the amnesic patients for 8 sec each. Retention was then tested after 10 min, 2 hr, and 30-32 hr using four different procedures for testing recognition memory. The different exposure times for the pictures succeeded in matching the performance scores of both groups of amnesic patients and the control subjects at the 10 min retention interval. Both groups of amnesic patients also performed similarly to control subjects at retention delays of 2 hr and 30-32 hr. In addition, performance was nearly identical, regardless whether recognition memory was assessed by asking subjects to select the new items or the old items. The findings emphasize the similarities between medial temporal lobe and diencephalic amnesia.     

Role of the medial temporal lobes in relational memory: neuropsychological evidence from a cued recognition paradigm

In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about targets that were presented either alone (no cue), with the originally presented cue (same cue), or with a cue that had been presented with a different target (recombined cue). Controls had higher recognition scores in the same cue than in the recombined cue condition, indicating that they benefited from the associative information provided by the same cue. By contrast, amnesic patients did not. This was true even for a subgroup of patients whose recognition performance in the no cue condition was matched to that of the controls. These data provide further support for the idea that the hippocampus plays a critical role in relational memory, even when associative information need not be retrieved intentionally.     

Reversible cold lesions of the parahippocampal gyrus in monkeys result in deficits on the delayed match-to-sample and other visual tasks

Two bilateral cooling probes were placed over the parahippocampal gyrus (pg) and the cortex just dorsolateral to it, the posterior inferotemporal gyrus (p.itg) in 4 Macaca fascicularis. Behavioral tests included: delayed match-to-sample (DMS); the acquisition and retention of single visual discriminations; the acquisition and retention of a concurrent visual discrimination task; and the retention of a spatial reversal task. During cooling of the pg and of the pg and p.itg together, there was a deficit at all delays on DMS. For both the single and concurrent visual discriminations, pg cooling produced an acquisition but not a retention deficit, although the acquisition deficit for the concurrent task was not significant at the 0.05 level. Cooling of p.itg had no significant effect on these tasks. No cooling had any affect on the spatial reversal task. It was concluded that pg serves as an important visual input into the anterior half of the itg for performance of DMS and the acquisition of visual discriminations. For several reasons, it was argued that the deficits were not caused by cooling of the hippocampus.     

Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients

Patients with frontal lobe lesions, amnesic patients with Korsakoff's syndrome, other (non-Korsakoff) amnesic patients, and control subjects were given tests of memory for temporal order. In the first experiment, subjects were presented with a list of 15 words and then asked to reproduce the list order from a random array of the words. In the second experiment, they were asked to arrange in chronological order a random display of 15 factual events that occurred between 1941 and 1985. In both experiments, patients with frontal lobe lesions were impaired in placing the items in the correct temporal order, despite normal item memory (i.e. normal recall and recognition memory for the words and facts). The two groups of amnesic patients exhibited impaired memory for temporal order as well as impaired item memory. Patients with Korsakoff's syndrome exhibited poorer temporal order memory than the other amnesic patients, despite similar levels of item memory. These findings demonstrate that patients with frontal lobe lesions have difficulty organizing information temporally. Patients with Korsakoff's syndrome, who have both diencephalic and frontal damage, have memory impairment together with a disproportionate deficit in memory for temporal order.     

Recognition memory for single items and for associations in amnesic patients

Recognition memory performance reflects two distinct processes or types of memory referred to as recollection and familiarity. According to theoretical claims about the two types of memory, single item and associative recognition tasks can be used as an experimental method to distinguish recollection and familiarity processes. Associative recognition decisions can be used as an index of recollection while memory for single items is mostly based on familiarity judgement. We employed this procedure to examine a possible dissociation in the memory performance of amnesic patients between spared single item and impaired associative recognition. Twelve amnesic patients, six with damage confined to the hippocampus proper, and six with damage elsewhere in the brain, were recruited for the present study. The findings showed that hippocampal amnesics exhibit relative sparing of single item learning but are consistently deficient in the learning of all kinds of between-item associations. These results are consistent with the view that hippocampal formation contributes differently to declarative tasks that require recollective or familiarity processes.     

Processing and short-term retention of relational information in amnesia

In a recent eye-movement study [Psychol. Sci. 11 (2000) 454], amnesic patients failed selectively to exhibit long-term effects of memory for the relations among the constituent elements of scenes. This failure could be due to a deficit specifically in long-term relational memory, as we have suggested; or in retention of relational information over any delay, whether involving perceptual processing and short-term maintenance or long-term memory, consistent with suggestions from recent studies of the hippocampus; or in on-line processing of relational information, as would occur in perceptual or feature binding. Here we show robust eye-movement effects of relations among elements of scenes in amnesia in a short-delay matching task, with the same materials and in the same amnesic patients in which long-delay conditions elicited failure. These findings document intact processing and short-term retention of relational information in amnesia, indicating that amnesia associated with hippocampal damage results in a relational memory deficit, specifically of long-term 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.     

Categorization and recognition performance of a memory-impaired group: evidence for single-system models.

Previous research has demonstrated dissociations between categorization and recognition performance in amnesic patients, supporting the idea that separate memory systems govern these tasks. However, previous research has also demonstrated that these dissociations are predicted by a single-system model that allows for reasonable parameter differences across groups. Generally, previous studies have employed categorization tasks that are less demanding than the recognition tasks. In this study, we distinguish between single-system and multiple-system accounts by testing memory-impaired individuals in a more demanding categorization task. These patients, just like previous amnesic participants, show a dissociation between categorization and recognition when tested in previously employed paradigms. However, they display a categorization deficit when tested in the more challenging categorization task. The results are interpreted as support for a single-system framework in which categorization and recognition depend on one representational system.     

Item Priming and Skill Learning in Amnesia

Abstract

This study employed a semantic decision-making task to examine both item priming and skill learning in amnesia, which traditionally have been demonstrated with separate tasks. Fourteen amnesic patients of mixed etiologies and 14 normal control subjects judged whether words represented animate or inanimate objects. One list was presented repeatedly on four continuous blocks of trials, and a new list was presented on the fifth block. For both groups, decision times decreased significantly from Block 1 to Block 5 (indicating skill acquisition) and increased significantly from Block 4 to Block 5 (indicating item-specific learning). The amnesic patients demonstrated a normal rate of skill learning, but a reduced magnitude of item priming. As expected, the amnesics had significantly impaired explicit memory of the implicitly learned items, as measured by recognition accuracy. The results suggest that both implicit and explicit learning of individual items is impaired in amnesia, despite normal semantic skill learning.     

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.     

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.     

Early cognitive decline in older adults better predicts object than scene recognition performance

There is an ongoing debate regarding the nature of memory deficits that occur in the early stages of mild cognitive impairment (MCI). MCI has been associated with atrophy to regions that process objects, namely perirhinal and lateral entorhinal cortices. However, it is currently unclear whether older adults with early MCI will show memory deficits that are specific to objects, or whether they will also show memory deficits for other stimulus classes, such as scenes. We tested 75 older adults using an object and scene recognition task with stimulus‐specific interference (i.e., exposure to irrelevant object or scene stimuli). We found an interaction (P = 0.05) whereby scores on the Montreal Cognitive Assessment, a neuropsychological test with high sensitivity to MCI, shared a stronger relationship with object recognition than with scene recognition performance. Interestingly, this relationship was not modulated by the stimulus category of interfering items. To further explore these findings, we also tested an amnesic patient (DA) with known medial temporal lobe damage. Like older adults with early signs of MCI, DA showed poorer object recognition than scene recognition performance. Additionally, his performance was not modulated by the stimulus category of interfering material. By demonstrating that object memory is more predictive of cognitive decline than scene memory, these findings support the notion of perirhinal and lateral entorhinal cortex dysfunction in the early stages of MCI. © 2016 Wiley Periodicals, Inc.