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Neuron

Review: Point/Counterpoint

Involvement of Medial Temporal LobeStructures in Memory and Perception

Mark G. Baxter1

1Department of Experimental Psychology, Oxford University, South Parks Road, Oxford OX1 3UD, UKDOI 10.1016/j.neuron.2009.02.007

Beginning approximately a decade and a half ago, it was suggested that some structures that are consideredto be part of the ‘‘medial temporal lobe memory system’’ could play a role in perception as well. The implica-tions of this view, interpreted broadly, are that medial temporal lobe structures may be understood as anextension of the ventral visual stream and that their functions cannot be described exclusively in terms ofmemory. Considerable evidence now supports the view that medial temporal lobe structures are involvedin nonmnemonic aspects of cognition, such as perception. This discovery allows for a fuller understandingof the involvement of these structures in mental phenomena than does a purely mnemonic account of theirfunction. See the related review by Suzuki, ‘‘Perception and the Medial Temporal Lobe: Evaluating theCurrent Evidence,’’ in this issue of Neuron.

tant role in online perceptual processing would falsify the stan-

dard view of MTL function.

This article will review, briefly, the evidence that has been

interpreted as demonstrating a role for MTL structures in percep-

tual functions as opposed to strictly mnemonic functions. It will

draw from studies in animals and humans, and from both exper-

iments, such as investigations of effects of lesions or temporary

inactivations, and correlational approaches, such as functional

neuroimaging and behavioral neurophysiology. The differences

in interpretation of these findings will also be discussed. As the

goal of these paired articles is to synthesize and integrate dispa-

rate views of a single literature, some possible avenues for future

work will be outlined, but these are also discussed more exten-

sively in the accompanying commentary (Suzuki and Baxter,

2009). A central theme running through this work is the extent

to which perceptual and mnemonic functions can be differenti-

ated from one another, both psychologically and behaviorally,

a topic to which I will return at the end of the paper.

Some Effects of Perirhinal Cortex LesionsAre Consistent with an Impairment in PerceptionAs far as I am aware, Eacott, Gaffan, and Murray (Eacott et al.,

1994) were the first to propose that the rhinal cortex (comprising

entorhinal and perirhinal cortex) may be involved in visual identi-

fication and perceptual function, similar to the laterally adjacent

cortical area TE. This study is of interest, therefore, for historical

reasons, but also because it serves to highlight some key issues

in the interpretation of findings from lesion studies that attempt

to address the role of defined cortical structures in cognition.

These authors trained macaque monkeys preoperatively on

several visual recognition memory tasks (delayed matching-to-

sample, DMS) in an automated apparatus. In this paradigm,

one or more visual objects (images on a computer screen) are

presented as ‘‘sample’’ objects, and then choice tests are

offered in which the monkey is allowed to select either the

sample object or a foil that was not presented during the sample

phase. In DMS, the monkey is rewarded for selecting the object

that appeared as a sample during the sample phase of that

Structures in the medial temporal lobe (MTL), including the

hippocampus and connected areas (entorhinal, perirhinal, para-

hippocampalcortex), havebeenproposed toconstitutea ‘‘medial

temporal lobe memory system’’ that is specialized for memory

functions in the mammalian brain. Although it is acknowledged

that these are not the only structures in the brain that are involved

in memory—for example, the medial diencephalon is critical for

memory (Aggleton and Mishkin, 1983; Mitchell et al., 2007; Victor

et al., 1989; Zola-Morgan and Squire, 1985)—the primary func-

tions of these areas are thought to be in storage and recall of facts

and events (Squire and Knowlton, 2000; Squire et al., 2004). In

particular, the MTL ‘‘(a) is principally concerned with memory,

(b) operates with neocortex to establish and maintain long-term

memory, and (c) ultimately, through a process of consolidation,

becomes independent of long-term memory’’ (Squire et al.,

2004, p. 279). The precise extent to which particular elements

of this system are differentially involved in specific aspects of

memory remains a topic of discussion: for example, are struc-

tures within this system further specialized for particular types

or modalities of memory, or do they work together as a unitary

memory system (Murray and Wise, 2004)?

Notwithstanding these considerations, a central tenet of this

characterization of the MTL is that its primary function is in

memory and not in other aspects of cognition (Squire et al.,

2004). However, beginning �15 years ago, experimental data

began to suggest that MTL structures may be involved in

perceptual functions as well. Thus, an alternative hypothesis

about the involvement of the MTL in cognition has emerged

which suggests that perceptual functions of these cortical areas

are just as important as their involvement in memory, or indeed

that apparently disparate mnemonic and perceptual functions

may arise from common computational mechanisms (Bussey

and Saksida, 2002; Murray et al., 2007). According to this view,

‘‘the perirhinal cortex’’ (a component of the MTL) ‘‘represents

information about objects for both mnemonic and perceptual

purposes’’ (Murray et al., 2007, p. 99). This differs from the stan-

dard view of MTL function, which holds that its main function is in

memory. Thus, establishing that MTL structures play an impor-

Neuron 61, March 12, 2009 ª2009 Elsevier Inc. 667

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particular test trial. In the more common delayed nonmatching-

to-sample, or DNMS, the monkey is rewarded for choosing the

other object that was not presented as a sample; see Figure 1

of Suzuki (2009). Eacott et al. (1994) found that monkeys with

rhinal cortex lesions were impaired in delayed matching-to-

sample performance, but this impairment was mitigated by

reducing the set size of objects from which the recognition

memory test was drawn and was eliminated entirely by reducing

the set of objects to two. Thus, monkeys with rhinal cortex

lesions could perform delayed matching-to-sample, a canonical

test of visual recognition memory, normally as long as the pool

from which the objects to be remembered were drawn was

very small (two). Moreover, with large sets of objects, deficits

could be seen even when the stimuli to be matched were pre-

sented simultaneously, or when a 0 s delay separated sample

and choice.

Although tasks such as DMS and DNMS are designed to study

memory rather than perceptual function, these findings were in-

terpreted as possibly suggesting a visual perceptual deficit,

rather than a mnemonic one, following lesions of the rhinal

cortex. Thus, some features of impaired and spared perfor-

mance may shed light on whether rhinal cortex damage impairs

perceptual function in addition to memory. Impaired perfor-

mance in the absence of memory demands (simultaneous and

0 s matching conditions) suggested an impairment in some

aspect of perceptual processing. The significance of this finding

has been criticized because a subsequent study reported that

monkeys with selective perirhinal cortex lesions were unim-

paired at learning a DNMS task with a 0.5 s delay between

sample and choice (Buffalo et al., 2000; see also Suzuki, 2009),

but because performance of these monkeys was not statistically

significantly different from that of controls at any delay (including

10 min delays between sample and choice), this result is difficult

to interpret. The statistical significance of the original finding of

Eacott et al. (1994) has also been questioned because it depends

on pooling data from several test conditions (Buffalo et al., 2000;

Suzuki, 2009).

Eacott et al. also showed that if the monkey was very familiar

with the objects to be remembered in the DMS task, because

they were used repeatedly across trials instead of being unique

from trial to trial, the rhinal cortex was apparently not required for

remembering which one had been seen in the sample trial. This

also supports a perceptual view of MTL function, because when

there was no demand on discrimination between the stimuli, the

rhinal cortex was also not necessary to remember them during

the delay between sample and choice. It might be argued that

this version of DMS no longer taxes visual recognition memory

but instead taxes working or recency memory. That is, rather

than simply recognizing whether a stimulus has been seen

before, the monkey must remember which of the two stimuli he

saw on the sample trial immediately preceding the current

choice trial in order to respond correctly. However, it is not

obvious why a similar strategy could not be applied to choice

trials with trial-unique stimuli.

At the time of the Eacott et al. (1994) study, it had been

demonstrated that lesions of entorhinal cortex, perirhinal cortex,

or both together impaired DNMS with trial-unique objects

(Meunier et al., 1993) and that lesions of rhinal cortex impaired

668 Neuron 61, March 12, 2009 ª2009 Elsevier Inc.

DMS but left object discrimination learning intact (Gaffan and

Murray, 1992). Furthermore, lesions of perirhinal and parahippo-

campal cortex together impaired DNMS in both visual and

tactual modalities, indicating that the deficit in DNMS perfor-

mance extended beyond the visual modality (Suzuki et al.,

1993). (For a review of the literature on stimulus recognition

leading up to the focus on the rhinal cortex, see Murray,

1996.) The finding that monkeys with rhinal cortex lesions could

succeed at DMS when tested with familiar stimuli and that

deficits in DMS could be seen with no or minimal memory

demands challenged the notion that the rhinal cortex was

responsible for all aspects of stimulus memory, although it

certainly was not an unambiguous demonstration of a perceptual

function of rhinal cortex.

A series of studies from Buckley and Gaffan extended this

initial observation. These authors reported that perirhinal cortex

lesions impaired concurrent discrimination learning with large,

but not small, sets of objects, as well as transfer of discrimination

learning between 2D and 3D representations of the same objects

and generalization of discrimination learning to new views of

familiar objects (Buckley and Gaffan, 1997, 1998a, 1998b).

These findings support a role for perirhinal cortex in being able

to perceptually identify objects, not just remember them. Again,

these data are not unambiguous. For example, it has been

argued that the set-size effects on discrimination learning simply

represent a magnification of a unitary impairment per problem

(Hampton, 2005) such that this impairment does not reach signif-

icance with a small number of discriminations but the additive

effect across a large number of discriminations creates a signifi-

cant difference from controls. Another criticism of these experi-

ments is that the impairment in transfer between 3D objects and

2D photographs of the same objects could just reflect an impair-

ment in discrimination learning, but this criticism can be rejected

on the basis of reanalysis of data from this experiment, showing

impairment in monkeys with perirhinal cortex lesions even on the

first trial of each problem (Buckley, 2005).

A subsequent experiment provided a more explicit test of

perceptual function by examining performance of monkeys

with perirhinal cortex lesions on oddity discriminations with

a number of different types of stimulus material (Buckley et al.,

2001). Monkeys with perirhinal cortex lesions were impaired on

oddity problems based on different viewpoints of objects,

degraded images of objects, human and monkey faces pre-

sented from different viewpoints, and visual scenes, but not on

problems based on color, shape, or size, irrespective of the diffi-

culty of particular problems, or same-viewpoint presentations of

human or monkey faces. Because the impairments were

observed on discriminations taxing complex object discrimina-

tion and not on difficult discriminations per se, this argues in

favor of a perceptual deficit rather than a problem with memory.

On the other hand, although associations with particular stimuli

and reward could not be used to solve the oddity problems

(because individual stimuli appeared equally often as the odd

one out and the foils), it could be argued that the impairment in

these tasks is expressed through learning as a consequence of

repeated exposure to particular objects, or association of

different views of the same stimuli with one another, and there-

fore has more to do with memory function than with perception

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(Suzuki, 2009). These limitations can be addressed, to some

extent, through the use of an oddity task with trial-unique stimuli

(discussed later in this article).

Formal Models of Perirhinal Cortex Involvementin Perceptual FunctionOne problem with all of these experiments is that the definition of

what constitutes ‘‘perception’’ is nebulous. Bussey and Saksida

(2002) devised a computational model in order to make explicit

predictions of how damage to perirhinal cortex would affect

performance in visual learning tasks, based on the idea that

the perirhinal cortex is a rostral extension of the ventral visual

stream that is specialized to process conjunctions of simple

perceptual features. In this model, the perirhinal cortex is at

the apex of a hierarchically organized system of visual cortical

areas. By virtue of its position in the hierarchy, the perirhinal

cortex is required to resolve discriminations with a high degree

of ‘‘feature ambiguity,’’ which occurs when the stimuli to be

discriminated have a large number of features in common.

However, this does not solve the problem of deciding what

a ‘‘feature’’ is. Some neuropsychological data bear on this point,

for example that ablations of the middle temporal gyrus

(including much of area TE) impair color discrimination but not

DNMS, whereas the reverse pattern is obtained with lesions of

perirhinal cortex (Buckley et al., 1997). Nevertheless, the model

does make explicit predictions about performance in a number

of tasks in which ‘‘features’’ are operationally defined. For

example, discrimination problems that can only be solved based

on a combination of features should require the perirhinal cortex

for their solution. One case of this is the biconditional discrimina-

tion problem, of the form AB+, CD+, BC�, AD�, where each

capital letter represents an individual feature and each pair of

letters represents an individual stimulus that is associated with

reward (+) or nonreward (�). When confronted with a stimulus

(for example AB), it is only possible to know whether that stim-

ulus is rewarded based on the combination of features A and

B, because A and B individually are each also part of nonre-

warded stimuli. Thus, a biconditional visual discrimination

problem requires processing of feature conjunctions—because

each individual feature is ambiguous—and should be impaired

by perirhinal cortex damage. In contrast, a discrimination

problem of the form AB+, CD+, EF�, GH� could be solved on

the basis of individual features: A only appears as part of the re-

warded stimulus AB. Because each feature is unambiguous, this

discrimination problem—which also requires learning about four

stimuli, each composed of two features—should not require

perirhinal cortex. An important property of these discrimination

problems is that they should place equal demands on memory,

because the number of stimuli to be associated with reward (or

nonreward) is the same in each case.

Bussey, Saksida, and Murray (Bussey et al., 2002) tested this

prediction directly in monkeys with lesions of perirhinal cortex,

by training them on visual discrimination problems in conditions

of minimal, intermediate, or maximal feature ambiguity (Figure 1).

On the view that perirhinal cortex is involved in visual learning

and memory irrespective of the degree of feature ambiguity

within the visual discrimination problem, one would predict that

perirhinal cortex lesions would produce equivalent impairments

in all three conditions. Alternatively, if perirhinal cortex is required

for solving visual discrimination problems only when resolution

of feature ambiguity is required, then the degree of impairment

should interact with the perceptual demands of the visual

discrimination problem. This latter pattern of performance is

exactly what was found (Figure 1). Importantly, the specification

of ‘‘feature ambiguity’’ as a critical factor in determining whether

perirhinal cortex is necessary for solving a visual task is consis-

tent with the observation that rotating or otherwise degrading

previously learned visual stimuli affects the performance of

control monkeys and monkeys with perirhinal cortex lesions

similarly (Hampton and Murray, 2002). Because these manipula-

tions do not affect the degree of feature ambiguity, they would

not be expected to produce any impairment after damage to

perirhinal cortex (and indeed they do not).

It may still be argued that this result tells us nothing about visual

perception, because the impairment is expressed in the context

of a learning problem. Alternatively, if the demands on learning

and memory are consistent between the various task conditions

(which they were in this study), then it is difficult to attribute any

observed deficits to impaired learning or memory. Instead, it

seems that the feature ambiguity manipulation is critical in deter-

mining whether the perirhinal cortex is involved in the task, rather

than any demands on learning and memory per se. Furthermore,

it is difficult to attribute the impairment to damage to cortical

areas outside of perirhinal cortex, both because the perirhinal

cortex lesions in Bussey et al. (2002) were extremely discrete

and because such damage (which would most likely be located

in laterally adjacent area TE) would produce impairments in visual

discrimination learning regardless of the degree of perceptual

ambiguity (Buffalo et al., 1998, 1999; Iwai and Mishkin, 1968).

Remarkably, the same pattern of impairment in discrimination

learning is seen in humans with temporal cortex lesions that

include the perirhinal cortex (Barense et al., 2005). Subjects in

this study with lesions limited to the hippocampus, who were

amnesic, were not impaired in any aspect of visual discrimination

learning, consistent with the effect of selective hippocampal

lesions in monkeys (Saksida et al., 2006). However, subjects in

the MTL lesion group were impaired as a function of the degree

of feature ambiguity within problems (Figure 2), just as monkeys

with perirhinal cortex lesions are. Related experiments have

used a ‘‘morphing’’ approach to create feature ambiguity

between visual stimuli and have examined impairments in

learning ‘‘morphed’’ discriminations in monkeys with perirhinal

cortex lesions, or in performance on probe trials of ‘‘morphed’’

stimuli created from ‘‘unmorphed’’ photographs that monkeys

have learned to discriminate. Again perirhinal cortex lesions are

without effect on single-pair discrimination learning of ‘‘un-

morphed’’ photographs, but impairments emerge as the degree

of feature ambiguity, created by ‘‘morphing,’’ increases (Bussey

et al., 2003, 2006). Some studies have reported similar findings

in humans with MTL damage (Lee et al., 2005b, 2007; cf. Levy

et al., 2005; Shrager et al., 2006), although there are concerns

about the anatomical specificity of MTL damage in patients that

are impaired on these tasks (discussed in the next section and

by Suzuki, 2009).

These investigations have focused on the involvement of peri-

rhinal cortex in perceptual function. It has been suggested that


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Figure 1. Effects of Manipulation of Feature Ambiguity on Discrimination Learning in Monkeys with Perirhinal Cortex (PRh) Lesions(Bussey et al., 2002)Example minimum and maximum feature ambiguity problems are illustrated. Each column shows a set of four problems, represented as a screen that would bepresented to the monkey. Each problem contains one rewarded stimulus (in the + column) and one unrewarded stimulus (in the� column); the left/right position ofthe stimuli was random for each trial. Each stimulus is composed of two grayscale photographs apposed to one another; the monkey’s task was to choose onepair of photographs by touching it. Each individual photograph composes a ‘‘feature’’ of the stimulus, so each stimulus is composed nominally of two features. Inthe minimum feature ambiguity problem, each feature appears only once as part of a stimulus, so each feature is either always rewarded or never rewarded. Forexample, the photograph of bandages is always part of a rewarded stimulus, and the photograph of the surgeon is always part of an unrewarded stimulus. In themaximum feature ambiguity problem, each feature appears as part of a rewarded stimulus and as part of an unrewarded stimulus, so it is impossible to solve thetask without relying on conjunctions of features because each individual feature is ambiguous. For example, the image of the ‘‘duck crossing’’ sign is part ofa rewarded stimulus in combination with the ‘‘Lot 6’’ sign, but part of an unrewarded stimulus when in combination with the picture of the child. Intermediatefeature ambiguity problems (not illustrated) have some features that are ambiguous and some that are not. Monkeys with PRh lesions are unimpaired at learningsets of discrimination problems with minimum feature ambiguity but are impaired at learning sets of problems with intermediate or maximum feature ambiguity.Thus, the perceptual qualities of the visual stimuli, rather than the memory demands of the task, determine whether an impairment is seen. Error bars indicate± SEM. Adapted from Figures 4, 6, and 7 of Bussey et al. (2002), by permission of Wiley-Blackwell.


and choice (Hartley et al., 2007). Although this latter result

suggests a more reliable impairment in very short-term memory

for spatial relationships rather than perception per se following

hippocampal damage, neither finding is consistent with the

viewpoint that the hippocampus is only required to maintain

memory beyond the capacity of short-term/working memory

(cf. Shrager et al., 2008). These findings, taken together, may

suggest a role for the hippocampus in the perception of scenes,

in the same manner as the perirhinal cortex is involved in the

other components of the MTL may also have perceptual func-

tions, such as the hippocampus. Humans with apparently selec-

tive hippocampal lesions were impaired at oddity discriminations

among virtual-reality ‘‘scenes’’ (Lee et al., 2005a; Figure 3). A

separate study of a different group of humans with hippocampal

lesions examined performance in a simultaneous matching-to-

sample task with topographical relations in visual scenes and

found impairments in two of the four patients, although all four

were impaired when a 2 s delay was introduced between sample

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Figure 2. Effects of Manipulation of Feature Ambiguity on Discrimination Learning in Humans with Hippocampal or MTL Damage(Barense et al., 2005)Two kinds of stimuli (‘‘barcodes’’ and ‘‘bugs’’) are illustrated, with three different problem sets in each. The problems are constructed in the same way as thoseused in testing monkeys with perirhinal cortex lesions (Figure 1). For the barcodes, the ‘‘features’’ are the left and right halves of each barcode; for the bugs, thefeatures are the body type and the legs. In the example illustrated with the bugs, in the minimum feature ambiguity condition, both body type and legs are unam-biguous; there are four different body types and four different leg shapes, and each body type or leg shape is part of an always-rewarded bug or a never-rewardedbug. Thus, it is possible to solve this discrimination by focusing on the presence or absence of individual features. In the intermediate feature ambiguity conditionillustrated, body type is ambiguous: there are only two different body types, and each body type is part of an always-rewarded bug or a never-rewarded bugequally often. In the maximum feature ambiguity condition, there are only two body types and two leg shapes, and all are ambiguous: each body type andleg shape is part of an always-rewarded bug and a never-rewarded bug. Thus, the conjunction of leg shape and body type must be used in order to solvethe problems, because each individual leg shape and body type is ambiguous. Performance of amnesic humans with either restricted hippocampal damageor larger MTL lesions including perirhinal cortex is shown in comparison with age-matched, neurologically intact control participants. Humans with hippocampallesions learn all the discrimination problems normally, regardless of feature ambiguity, but humans with MTL lesions are impaired as a function of feature ambi-guity. Error bars indicate ± SEM. Adapted from Figures 2 and 3 of Barense et al. (2005). Reprinted by permission of The Journal of Neuroscience.


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perception of objects (Murray et al., 2007). However, this hypoth-

esis remains speculative pending accumulation of further data,

in particular from studies in animals in which discrete hippo-

campal lesions can be produced experimentally. This is an

important avenue for future investigations.

What Are the Criticisms of a Role for MTL Structuresin Perception?Some criticisms of these experiments have already been alluded

to. They fall primarily into two categories, related to anatomical

and cognitive specificity of impairments. First, it has been argued

that the extent of brain damage in amnesic patients who are

impaired on ‘‘perceptual’’ tasks has not been adequately delin-

eated, and damage outside the MTL may be able to account

for their perceptual impairments without needing to hypothesize

a role for MTL structures in perceptual function. For example,

Shrager et al. (2006) have suggested that patients tested by

Lee, Barense, and colleagues (Barense et al., 2005; Lee et al.,

2005b) may have damage in temporal cortical structures outside

the MTL that can account for their perceptual impairments (see

also Suzuki, 2009). Recent volumetric analyses of the extent of

Figure 3. Performance of OddityDiscrimination Problems, with Same andDifferent Views of Faces and Scenes, inHumans with Hippocampal or MTL DamageParticipants view displays of four objects, threeviews of the same face or scene and one ofa different face or scene, and are asked to identifythe ‘‘odd one out.’’ In ‘‘same-view’’ problems, thethree images of the same face or scene are pre-sented from the same viewpoint; in ‘‘different-view’’ problems, the three images of the sameface or scene are presented from different view-points. All participants find it easy to identify theodd stimulus in ‘‘same-view’’ face and sceneoddity problems. Humans with hippocampallesions are unimpaired relative to their age-matched controls (‘‘young controls’’) on different-view face oddity, but are impaired in different-view scene oddity. Notably, controls find thesekinds of problems equally difficult, so this is notthe result of a task-difficulty effect. Humans withMTL damage that extends beyond the hippo-campus into the adjacent cortex (including perirhi-nal cortex) are impaired in both face and sceneoddity problems with different views, relative totheir age-matched controls (‘‘elderly controls’’).Error bars indicate ± SEM. Adapted from Figures3 and 6 of Lee et al. (2005a) by permission.

lesions in this patient population support

the conclusions drawn from visual ratings

of MRI scans (A.C. Lee et al., 2008,

Society for Neuroscience, abstract;

A.C.H. Lee, personal communication,

July 14, 2008), so it is unlikely that there

is undetected damage in these patients

that has not been described.

In any case, this is an issue with any

lesion analysis in human patient popula-

tions, where the lesion extent is variable

and, in the case of neurodegenerative

diseases, progressive. The striking similarity between the perfor-

mance of monkeys with discrete perirhinal cortex lesions and

that of humans with broader MTL damage on nearly identical

tasks is compelling in terms of localization of the perceptual

deficits to the MTL. Converging information from fMRI in neuro-

logically intact humans reveals perirhinal cortex activation corre-

lated with oddity judgments (Devlin and Price, 2007; Lee et al.,

2008) as well as for other aspects of object processing associ-

ated with feature ambiguity (Tyler et al., 2004; Moss et al.,

2005) that are impaired by MTL lesions (Moss et al., 2005).

This correlational evidence provides confirmation of the neuro-

anatomical locus of these functions in intact brains, because it

is not possible to localize function with this degree of specificity

based on lesions in human patients. Although neurophysiolog-

ical data have indicated similarity in visual properties of neurons

in perirhinal cortex and laterally adjacent area TE (Suzuki, 2009),

these firing correlates may reflect information passing between

these areas. Disruption of activity in perirhinal cortex or TE while

recording in the complementary area could help resolve this

question (see, for example, Higuchi and Miyashita, 1996). Two

other points are noteworthy in this context. First, to the extent


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that damage outside of core MTL structures accounts for

perceptual impairments in visual discrimination and oddity tasks

in humans with MTL damage, it is not clear why this damage

would cause impairments that are related to the degree of

feature ambiguity in the stimuli that are presented. Second, there

is little variability in the performance of the MTL patients whose

lesion localization has been questioned (those tested by Lee

et al., 2005a, 2005b), despite differences in the extent of damage

outside of core MTL structures (Suzuki, 2009). For example, if

lateral temporal damage is responsible for the discrepant perfor-

mance of MTL patients in Lee et al. (2005b) and Shrager et al.

(2006), then the subject with the most lateral temporal damage

(MTL1) should be dramatically worse than the other two MTL

patients on the perceptual tasks, but this is not the case.

The second criticism is that cognitive impairments that are

apparently perceptual are instead the result of impaired memory.

There are at least two ways in which impaired learning and

memory could account for effects ascribed to impaired percep-

tion. First, it could be the case that feature-ambiguous discrimi-

nation problems are simply more difficult and therefore unmask

a subtle impairment in visual discrimination learning caused by

perirhinal cortex lesions. But Buckley et al. (2001) show that

there is no relationship between discrimination difficulty, per

se, and impairment (or lack thereof) in their monkeys with perirhi-

nal cortex lesions, so it cannot be that oddity problems that

require ‘‘object identification’’ or discrimination of feature ambi-

guity are simply more difficult. Similarly, color and size discrimi-

nations that are equally difficult to feature-ambiguous discrimi-

nations were learned normally by monkeys with perirhinal

cortex lesions (Bussey et al., 2003). Second, because the impair-

ments in oddity discrimination in monkeys with perirhinal cortex

lesions occur over the course of repeated presentations of

oddity problems, they could simply reflect an impairment in

visual discrimination learning or long-term familiarity with the

stimuli. But learning is not apparent across blocks of oddity

problems in humans (Lee et al., 2005a). Similarly, when monkeys

learn to discriminate a pair of target images and perception is

probed with probe trials with morphed stimuli, learning is not

seen across probe trials (Bussey et al., 2003, 2006). It seems

imparsimonious to hypothesize a memory deficit which is not

strong enough to impair discrimination learning but results in

impairment in probe trials as a function of feature ambiguity (Su-

zuki, 2009). When the memory demands are constant across the

various task conditions and the only variable that is manipulated

is feature ambiguity, it is difficult to explain oddity discrimination

impairments and impairments in discriminating high feature-

ambiguity stimuli in terms of anything other than a perceptual

impairment (Murray et al., 2005). The argument that higher

feature-ambiguity discriminations place a greater demand on

memory because the degree of detail required to discriminate

the stimuli is greater (Suzuki, 2009) is simply an appeal to

a task difficulty explanation, and there is ample evidence that

monkeys (and humans) with MTL damage are not impaired on

difficult discrimination problems. Nevertheless, these are prob-

lems with any procedure in which trial-unique stimuli are not pre-

sented. Recent studies in human patients with MTL damage

(Barense et al., 2007) and rats (Bartko et al., 2007), which also

find impairments in oddity discrimination in high feature-ambi-

guity conditions using trial-unique stimulus presentation, can

address this limitation.

It is also notable that different investigators have reported

different results from patients with MTL lesions on apparently

similar tasks. For example, Stark and Squire (2000) report intact

oddity-discrimination performance in two amnesic patients with

large MTL lesions, whereas Lee et al. (2005a) report oddity-

discrimination impairments in their amnesic patients. These

differences have been attributed by some, as mentioned, to

differences in the location and specificity of MTL lesions. It is

also worth comparing the performance of control subjects

across different investigations on various tasks. For example,

the control subjects in Stark and Squire (2000) find some of the

perceptual tasks as difficult as the amnesic patients do in Lee

et al. (2005a). Both studies tested oddity discriminations with

displays of six faces, five orientations of one face and a sixth

different face (experiment 1 of Lee et al., 2005a, and task 7 of

Stark and Squire, 2000) using apparently nearly identical proce-

dures. The control subjects in Stark and Squire (2000) perform at

�68.2% correct on face oddity and the MTL subjects at 57.3%

correct (estimated from their Figure 4). In Lee et al. (2005a), the

control subjects perform at �88.3% correct on face oddity and

the MTL subjects at 62.3% correct (estimated from their

Figure 4). Thus, some apparent differences in results between

laboratories may relate to the control data that are used for

comparison, rather than the effects of MTL damage per se,

although in other cases performance of control subjects is well

matched across studies (Lee et al., 2005b; Shrager et al.,

2006; discussion in Suzuki, 2009). This is an issue that is difficult

to address given geographic, demographic, and other differ-

ences between patient populations that are tested by different

groups of investigators. Ideally, investigators would attempt to

make their patients and control subjects accessible to testing

by other research groups, in an attempt to exclude possible

methodological or other confounds that might complicate

comparison of results across different laboratories. (For

example, the surgical method used to produce hippocampal

damage in monkeys was excluded as a factor for interlaboratory

differences in effects of hippocampal damage on recognition

memory by testing monkeys operated by one group of investiga-

tors in the laboratory of another group of investigators [Zola-

Morgan and Squire, 1986].) Other differences are more difficult

to resolve: Shrager et al. (2006) used trial-unique presentations

of ‘‘morphed’’ discriminations, using similar stimuli to Lee et al.

(2005b), and failed to find impairments in their population of

amnesic patients. This may be unique to the ‘‘morphing’’

discriminations, which may be solvable based on identification

of single features when simultaneously presented pictures are

compared, and thus do not adequately tax feature ambiguity

(M.D. Barense, personal communication, May 9, 2008; Figure 4).

I have discussed arguments for and against the interpretation

of behavioral impairments after MTL damage as a consequence

of impaired perception rather than memory. Another argument

against a role for the MTL in perception is that preserved perfor-

mance in some tasks is indicative of intact perception after MTL

damage. For example, preserved performance at short delays in

recognition memory tasks is often taken as evidence that

subjects have intact perceptual function, attention, motivation,


Neuron


Figure 4. Even Difficult ‘‘Morphed’’Discrimination Problems, Designed to TaxFeature Ambiguity, May Be Solvable Basedon Individual FeaturesA subject asked to judge which of two blendedimages (on the left and right) is most similar tothe middle image may be able to do so by focusingon individual features of the images, potentiallylimiting the utility of these types of problems for as-sessing the impact of MTL damage on perception.In the top row, the baseball player’s belt is clearlymore apparent in one blended image than theother (red arrowheads), rendering this discrimina-tion a shading judgment rather than a test offeature ambiguity. Similarly, in the bottom row,the darkness of the animal’s nose (arrowheads)provides a single feature that can be focused on.Top row adapted from Figure 5 of Levy et al.(2005) by permission of Cold Spring Harbor Labo-ratory Press (ª 2005). Images in bottom rowprovided by Andy C.H. Lee.


controversies here. However, a role for MTL in perception may

allow for an explanation of some experimental observations

that a purely mnemonic account of MTL function does not.

The ‘‘perceptual-mnemonic’’ (Bussey and Saksida, 2002;

Murray et al., 2007) hypothesis may provide a framework to

understand effects of MTL damage on tasks like visual discrim-

ination learning that cannot readily be accommodated in terms

of an exclusive role for the MTL in memory. According to this

view, neurons in the MTL encode representations of objects or

scenes that are necessary for both perception and memory.

The prevailing view of MTL involvement in memory is that the

MTL is specialized for declarative memory, that is, memory for

facts and events that in humans is consciously accessible

(Squire and Knowlton, 2000; Squire and Zola-Morgan, 1991). It

has been difficult, a priori, to decide whether a learning and

memory task is ‘‘declarative’’ or not without making reference

to the performance of amnesic patients on the task (or the perfor-

mance of animals with lesions of structures within the MTL).

Of course, this leads to problems with circularity of definitions,

which have been previously discussed (Morris, 1984; Nadel,

1992). For example, visual discrimination learning has been sug-

gested to be ‘‘declarative’’ on the basis that it is rapidly acquired

(Teng et al., 2000). However, discrimination problems that are

learned rapidly do not necessarily require the hippocampus

(Broadbent et al., 2007; Jonasson et al., 2004). Indeed, the

maximum feature ambiguity discrimination problems tend to

be learned more slowly, yet these are the ones that are impaired

by MTL lesions. Thus, there is nothing ‘‘declarative’’ or not about

visual discrimination learning, although such problems may be

acquired by different learning mechanisms, some slow and

some fast, perhaps in parallel in neurologically intact humans

(Bayley et al., 2005; Hood et al., 1999). Although it is difficult to

account for these data with a purely mnemonic hypothesis of

MTL function, they are readily explained by the ‘‘perceptual-

mnemonic’’ view.

Another advantage of this point of view is that it may explain

the dependence of memory impairments in amnesia on stimulus

modality that are difficult to accommodate in other ways.

and understanding of the task rules, in addition to intact memory

at short delays between sample and choice. There are several

difficulties with this argument. First, extensive training at short

delays is often required to achieve good performance at short

delays between sample and choice in monkeys with MTL

lesions, whether they were trained preoperatively in recognition

memory or not (e.g., Meunier et al., 1993; Zola-Morgan et al.,

1989). This may introduce a bias in performance favoring the

short delay that is trained extensively (Ringo, 1993). Second,

monkeys with MTL damage may fail to learn recognition memory

tasks even after extensive training (e.g., Suzuki et al., 1993), chal-

lenging the conclusion that the only effect of these lesions is on

intermediate- or long-term memory. Third, even when there are

no differences in performance at short delays, typically the

objects used are not designed to tax the hypothesized percep-

tual functions of the MTL (that is, they are not explicitly feature

ambiguous). Finally, the delay dependence of many MTL lesion

effects on recognition memory performance may be related to

the use of a percent correct scale of measurement, because

these effects are not delay dependent when analyzed in a d’

metric (Baxter and Murray, 2001; Ringo, 1988, 1991). Thus, the

effect of MTL lesions on performance of tasks like DNMS may

not necessarily reflect memory impairment. It may be possible

to explain these lesion effects in terms of a similar computational

mechanism to that which is involved in resolution of feature

ambiguity in discrimination learning (Cowell et al., 2006).

How Does a Perceptual/‘‘Perceptual-Mnemonic’’View of MTL Function Advance the Understandingof the Organization of Brain Systems for Cognition?Why might it be useful to consider that MTL structures, including

perirhinal cortex and hippocampus, may play a role in perception

as well as in memory? Considerable effort has been devoted to

identifying which structures in the MTL are essential for memory

function, as well as the potential for different MTL structures to be

involved in different aspects of memory (for instance, semantic

versus, episodic, or recognition versus recall). This remains

extremely controversial, and I will not attempt to address these

Neuron


Patients with hippocampal damage show intact perceptual

learning and categorization of faces, but not of virtual-reality

scenes (Graham et al., 2006). Not only are these tasks thought

to be ‘‘nondeclarative’’ and therefore independent of the MTL,

but there is no reason to expect the hippocampus to be involved

in memory for scenes but not faces if it has a general role in

declarative memory. Similarly, recognition memory for scenes

is impaired in patients with amnesia consequent to hippocampal

damage, but recognition memory for faces is not (Bird et al.,

2008; Taylor et al., 2007). A dissociation between impaired

recognition memory for words, but intact recognition memory

for faces, in patients with hippocampal damage has been attrib-

uted to hippocampal involvement in providing contextual

support for recognition of familiar items (Bird and Burgess,

2008). A role for the hippocampus in representation of spatial

or contextual information, used for both perception and memory,

is able to account for all of these observations.

It is clear that many questions remain to be resolved in trying to

understand the contributions of MTL structures to memory and

perception. However, progress in this area depends on at least

acknowledging the possibility that the involvement of MTL struc-

tures in cognition extends beyond the domain of memory. It is

common to argue that ‘‘perception’’ is intact after MTL damage

because humans or animals with MTL damage perform normally

on some tasks that are thought to tax perceptual functions. For

example, because monkeys with MTL damage can perform

the DNMS task at short delays with minimal memory demand

(Suzuki, 2009), or because rotating or masking visual stimuli in

monkeys with perirhinal cortex lesions is no more deleterious

to their performance than it is in controls, then their perceptual

functions must be intact (Buffalo et al., 1999; Hampton and Mur-

ray, 2002; Squire et al., 2004). But, as indicated earlier, these

tasks do not adequately tax the perceptual functions that MTL

structures are thought to mediate. The use of feature ambiguity

to tax perceptual discriminations among visual stimuli may tap

into the role of perirhinal cortex in mediating object identification

function more generally (Murray et al., 2000). The finding that

some aspects of perceptual function are intact after perirhinal

cortex damage no more excludes a role for perirhinal cortex in

perception, than the finding that some aspects of memory func-

tion are intact after hippocampal damage excludes a role for the

hippocampus in memory.

The strong version of the ‘‘perceptual-mnemonic’’ view of MTL

function argues that it is not useful to distinguish between

‘‘perception’’ and ‘‘memory’’ as psychological functions, to the

extent that they may arise from a single mechanism at the neural

level. Most would agree that a difference in forgetting rate, when

it has been established that information has been acquired to the

same degree, reflects an impairment in memory rather than

perception. Similarly, most would agree that tasks in which

performance depends on simultaneous comparison of trial-

unique stimuli tax perceptual function rather than memory.

However, these ‘‘folk psychological’’ views of cognition may

impede progress toward understanding how cognitive functions

arise from the physiological activity of the brain (e.g., Bussey,

2004). It is challenging to move beyond these views, especially

given the compelling phenomenology of densely amnesic

patients with MTL lesions, who present with amnesia rather

than agnosia. Nevertheless, the accumulation of evidence that

patients with MTL damage have cognitive impairments that

extend beyond memory forces a reconsideration of the view

that the function of the MTL is exclusively concerned with

memory. Rather than trying to determine the location in the brain

of a sharp line between perception and memory, it may be worth

viewing MTL function in terms of representational capacities that

are used for both cognitive processes (Murray et al., 2007).

Indeed, it is likely that the influence between apparently separate

processes of ‘‘perception’’ and ‘‘memory’’ is bidirectional, with

stored representations affecting online sensory processing

(e.g., Hochstein and Ahissar, 2002). The recent demonstration

that patients with selective hippocampal damage are impaired,

not just in recalling past events, but in imagining future ones

(Hassabis et al., 2007) suggests that even the hippocampus,

for decades the single structure in the brain most closely identi-

fied with memory function, may also be necessary for the

perception and representation of episodes, not merely their

storage and recall. These investigations promise a fuller under-

standing of how brain function gives rise to the phenomena of

mind.

ACKNOWLEDGMENTS

I thank Morgan Barense, Tim Bussey, David Gaffan, Andy Lee, and ElisabethMurray for helpful comments and discussion. My research is supported by theWellcome Trust.

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