Knowing where things are: Parahippocampal involvement in encoding object locations in virtual...

Knowing Where Things AreParahippocampal Involvement in EncodingObject Locations in Virtual Large-Scale Space

E A Maguire and C D FrithInstitute of Neurology London

N Burgess J G Donnett and J OrsquoKeefeUniversity College London

Abstract

The involvement of the medial temporal-lobe region inallocentric mapping of the environment has been observed inhuman lesion and functional imaging work Cognitive modelsof environmental learning ascribe a key role to salient land-marks in representing large-scale space In the present experi-ments we examined the neural substrates of the topographicalmemory acquisition process when environmental landmarkswere more specically identiable Using positron emissiontomography (PET) we measured regional cerebral blood owchanges while normal subjects explored and learned in a vir-tual reality environment One experiment involved an environ-ment containing salient objects and textures that could be usedto discriminate different rooms Another experiment involved

a plain empty environment in which rooms were distinguish-able only by their shape Learning in both cases activated anetwork of bilateral occipital medial parietal and occipito-temporal regions The presence of salient objects and texturesin an environment additionally resulted in increased activity inthe right parahippocampal gyrus This region was not activatedduring exploration of the empty environment These ndingssuggest that encoding of salient objects into a representationof large-scale space is a critical factor in instigating parahippo-campal involvement in topographical memory formation inhumans and accords with previous studies implicating parahip-pocampal areas in the encoding of object location

INTRODUCTION

Study of the nonhuman medial temporal lobe suggest ithas a signicant role in processing spatial informationthat is independent of the location or orientation of anavigating animal (ie processing spatial information inan allocentric frame of reference) The hippocampus hasbeen proposed to maintain a cognitive map of the spatiallayout of learned environments (OrsquoKeefe amp Nadel 1978)and complex spike cells within the rat hippocampushave been found to exhibit spatially localized ring(OrsquoKeefe amp Dostrovsky 1971) In nonhuman primatesthe activity of hippocampal neurons has also been re-lated to spatial processing (Feigenbaum amp Rolls 1991Rolls Cahusac Feigenbaum amp Miyashita 1993) withOrsquoMara Rolls Berthoz amp Kesner (1994) and RollsRobertson amp Georges-Franccedilois (1995) recently reportingsuch activity during whole-body motion in both re-strained and freely moving monkeys Removal of thehippocampus in monkeys also results in decits on spa-tial delayed response with delays of 30 sec or more(Zola-Morgan amp Squire 1985) and with spatial delayedresponse involving the memory for two positions (An-

copy 1998 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 101 pp 61ndash76

geli Murray amp Mishkin 1993 Parkinson Murray ampMishkin 1988)

In humans lesions of the medial temporal lobe par-ticularly on the right are reported to impair memory forthe spatial location of objects (Pigott amp Milner 1993Smith amp Milner 1981 1989) Interestingly FeigenbaumPolkey and Morris (1996) using a computerized golf taskwith temporal lobectomy patients found both left andright temporal lesions resulted in impairment in spatialmemory Goldstein Canavan and Polkey (1989) foundleft and right temporal lobectomy patients were able toperform a design recall task devised to assess egocentricstrategies but patient groups scored lower than controlson the nonegocentric tasks However human spatialmemory studies and indeed most monkey work exam-ines spatial processing within an egocentric (ie relativeto the body) frame of reference The real world incontrast comprises environments where all points inspace cannot be perceived directly in one eld of viewrequiring humans to form allocentric cognitive repre-sentations of spatial layouts Maguire Burke Phillips andStaunton (1996) directly examined topographical mem-ory or spatial memory in a real-world context by show-

ing temporal lobectomy patients rst-person perspectivelm footage of navigation through an urban area andexamining learning and memory along a range of pa-rameters Decits in topographical memory were iden-tied in patients with unilateral medial temporal-lobelesions on both the left and the right where generalneurological and neuropsychological functioning was in-tact These ndings correspond to previously reportedcases of topographic difculties after damage encom-passing the parahippocampal region (Habib amp Sirigu1987) and similar impairments in cases with bilateral andunilateral lesions involving the temporal lobe (De Renzi1985 Landis Cummings Benson amp Palmer 1986)

Recent functional imaging work has attempted to pro-vide further insights into the precise neural substrates ofspatial memory in humans Owen Milner Petrides andEvans (1995) using positron emission tomography (PET)found activation of the caudal region of the right medialtemporal region associated with the encoding of objectlocations from an array on a computer screen but notwith the encoding of location alone Recall of objectlocation was associated with activation of the right para-hippocampal gyrus Moscovitch Kapur Kohler amp Houle(1995) in contrast found activation of the supramarginalgyrus to be associated with the recall of object locationHowever in the latter case there were only three objectlocations per trial whereas the Owen study had eightper trial Thus differences in memory load andor spatialarray complexity may be the basis of these differentactivations Neither the Owen nor Moscovitch studiescapture the allocentric frame of reference that is thebasis of topographic representations of large-scale spaceGiven the restrictive environment of brain scanners ex-amining topographical memory or way-nding necessi-tates the use of novel stimuli Maguire Frackowiak andFrith (1996) used PET to measure regional cerebralblood ow (rCBF) while normal subjects memorizedlm footage depicting either navigation in an urban areaor nonnavigation events in a similar environment Onlythe viewing of the navigation lm footage resulted infocal and signicantly increased activation of the para-hippocampal cortex and hippocampus on the right andthe parahippocampal cortex on the left Aguirre DetreAlsop and DrsquoEsposito (1996) report similar parahippo-campus activations with a computerized topographicallearning task using functional magnetic resonance imag-ing (fMRI) It would seem therefore from human lesionand functional imaging work that the parahippocampalgyrus bilaterally is critical for topographical memoryformation whereas the functional signicance of thehuman hippocampus proper is currently less-well spe-cied

In the present PET study we used computer-simulatedrst-person virtual reality environments to simulate navi-gation in large-scale space Elements of these environ-ments were manipulated in order to examine moreprecisely the neural correlates of topographical memory

acquisition This approach has the added advantage ofaffording more naturalistic self-directed exploration onthe part of subjects In the rst experiment the virtualenvironment included specic objects as well as variedtextures and colors In the monkey two distinct andfunctionally specialized cortical pathways have beenidentied for object processing an occipito-temporalpathway for the recognition of objects and an occipito-parietal pathway for processing spatial relations amongobjects (Mishkin Ungerleider amp Macko 1983) In PETstudies there has been some support for homologousprocessing pathways in humans (Haxby et al 1991 Mar-tin Wiggs Ungerleider amp Haxby 1995 Price MooreHumphreys Frackowiak amp Friston 1996) However ob-ject recognition studies generally examine objects lo-cated in egocentric space In particular this does notadequately capture the spatial essence of objects inlarge-scale space that must be located in an allocentricframe of reference The neural correlates of object en-coding in the context of topographical memory forma-tion remain unspecied Based on previous studies wepredicted that encoding of the environment with ob-jects would activate areas known to be involved inobject identication (Haxby et al 1991 Sergent Ohta ampMacDonald 1992) and the topographical memory en-coding would activate the medial temporal region in linewith Maguire Frackowiak et al (1996) and Aguirre et al(1996)

All previous topographical memory studies have usedenvironments that had objects present In a secondexperiment in this study the layout of the virtual en-vironment while broadly similar to that in the rst ex-periment was effectively free of salient objects andtextures Differences in the shape of rooms were theonly distinguishing features that enabled subjects to en-code meaningful environmental information The pur-pose of using this environment was to extend theinvestigation of the topographical memory acquisitionprocess beyond previous studies by examining its neuralsubstrates where environmental inputs were more spe-cically identiable This is the rst instance in functionalimaging where topographical learning based only ongeometric information has been examined Given theOwen et al (1995) nding of activation in the rightcaudal medial temporal region associated with objectlocation on a computer screen but not location aloneone might expect there to be no medial temporal activ-ity associated with the encoding of the featureless envi-ronment However the Parkinson et al (1988) and Angeliet al (1993) reports of decits in hippocampectomisedmonkeys in both place-only and object-in-place spatialdelayed responses suggest that the medial temporal re-gion may be implicated in the spatial representationirrespective of the presence of objects Hermer andSpelke (1994) found that young children reorient them-selves in accord with geometric or shape informationfrom the environment and OrsquoKeefe and Burgess (1996)

62 Journal of Cognitive Neuroscience Volume 10 Number 1

report evidence of geometric determinants of hippo-campal place elds in rats Thus activity in the medialtemporal region associated with the encoding of theplain environment in Experiment 2 might be expected

We examined the encoding of the two environmentsin separate experiments using naive subjects for eachtaking behavioral measures post-scanning (way-ndingperformance within the virtual environments) and dur-ing PET scanning using rCBF as an index of change inlocal neuronal activity Separate groups of subjects wereused for the two experiments because of the signicantprobability of interference and cross-cueing between thetwo environments if they were presented to the samesubjects in one scanning session Because of the com-plexity of virtual reality environments the design ofsuitable baseline or control tasks is particularly difcultThe baseline tasks employed in the present study weredesigned to control for basic eye movements and motor(joystick) activity It was also intended that comparisonof the experimental tasks with the low-level baselinetasks would facilitate examination of the distributed net-work of regions necessary for task performance Con-trasting the main task comparisons in the two studieswould then enable more specic inferences about theneural substrates of the varying element between thetwo experiments (ie the presence or absence of ob-jects)

RESULTS

Experiment 1mdashEnvironment with Objects

Subjects controlled their movement within the virtualenvironment with a joystick There were two conditionsIn the rst condition subjects had to explore and memo-rize an environment containing objects (one per room)and varied textures and were told that they would betested on their ability to nd the objects In the second(control) condition the screen was lled with successiveimages similar to the textures from the environmentSome of these images remained stationary and othersmoved either to the left or the right Subjects wereinstructed to move the joystick forward if the image wasstationary left if it was moving left or right if it wasmoving right Five subjects participated in Experiment 1The two tasks were each replicated six times The orderof tasks was alternated within subjects and the startingcondition was alternated between subjects Each taskreplication lasted 100 sec (encompassing the 90-sec du-ration of scanning acquisition)

Behavioral Data

Figure 1a depicts the ground plan of the environmentwith the ve differently shaped areas and their associ-ated object locations (Figures 1b and c are describedunder ldquomethodsrdquo) The average number of areas visited

during each scan of the environment exploration condi-tion was 477 (SD 048) Across the six scans of theenvironment condition the number of object-containingareas visited remained relatively constant (range 46ndash5SD range 089ndash114) Subjectsrsquo reports of explorationstrategies reveal that they did not visit every objectduring every scan but restricted exploration to thoseareas that they were most unsure of or those not yetvisited Post hoc examination of the 30 scans (5 subjectstimes 6 environment scans) of the environment condi-tion showed that subjects employed both systematic leftor right turning (13 scans) and less-constrained (17scans) strategies during exploration Two subjects usedpredominantly leftright exploration and three subjectsemployed free exploration strategies Post-scan testing ofthe ability to way-nd in the environment revealed threesubjects to be performing at ceiling level one just belowceiling and one to be performing at chance level In thislatter case the subject used leftright exploration duringevery scan although another subject who used the samestrategy in ve of the six scans performed at ceilingFinally subjects had to sketch a map of the environmentin all cases sketch maps were inclusive for objects andaccurate for object locations within each area of theenvironment Four of the ve sketch maps also accu-rately represented the spatial relationships between theobject-containing rooms The sketch map of the subjectwho performed at chance on the post-scan way-ndingtask less accurately depicted the spatial relationshipsbetween areas

PET Data

Initially a descriptive data-led eigenimage analysis wasperformed to characterize the rCBF changes in terms ofdistributed brain systems (Friston 1994) The principaleigenvector for the analysis of Experiment 1 is presentedin Figure 2 The eigenvector clearly shows positive load-ing on scans corresponding to exploration of theenvironment and negative loading on those scans corre-sponding to random texturecolor images The formercorrelates with changes in activity in occipital and oc-cipito-temporal regions and also includes the posteriortemporal regions The rst eigenvector accounts for691 of the variance in the data and clearly reects thatexperimental manipulation by the tasks is the main con-tributor to that variance

Areas of signicant change in brain activity were de-termined using appropriately weighted contrasts be-tween the task-specic conditions and the t statistic(Friston et al 1995) The rCBF increases associated withthe principal task comparisons are reported in Table 1(part 1) and areas of peak activations are superimposedonto template MRI scans in Figure 3 Comparison of theactivity during exploration of the environment with ran-dom colortexture images revealed bilateral activity inprestriate regions bilateral occipito-temporal areas the

Maguire et al 63

Figure 1a Aerial view (neverseen by subjects) of the envi-ronment containing objectsClose-set lines indicate stairs

Figure 1b Subjectrsquos view ofthe central room of the envi-ronment with objects (actualenvironment in color)

Figure 1c Instructions dis-played before entering the en-vironment showing theobjects (actual objectspresented in color)


cerebellum and the precuneus Notably there was alsosignicant activation of the right parahippocampal gyrusin this comparison The reverse contrasts showed deac-tivation bilaterally in the superior temporal gyrus (peak

52 10 8 Z = 999)A correlation analysis with scan serial position as the

correlate showed that activity signicantly increasedacross the scans of the environment task in the cingulatecortex ( 14 2 48 Z = 425) and decreased in the rightsupramarginal gyrus (54 50 32 Z = 578) Analysis ofthe scans across subjects dependent on explorationstrategy employed showed that free exploration com-pared to systematic leftright strategy was associatedwith signicant rCBF change in the cingulate cortex (18

26 28 Z = 466) The converse comparison showed

rCBF change in the right middle frontal gyrus (44 16 44Z = 463)

Experiment 2mdashEmpty Environment

Six naive subjects participated in the second experimentThe three experimental conditions were (1) explore andmemorize an empty and plain environment (2) explorea featureless large open room (control 1) and (3) movethe joystick to keep random colors changing on thescreen (control 2) The three tasks were each replicatedfour times The order of the tasks was counterbalancedwithin and between subjects Each task replication lasted100 sec (encompassing the 90-sec duration of scanningacquisition)

Figure 2 Principal eigenvec-tor from the data-led eigen-image analysis of Experi-ment 1 (objects) showingclear task effects accountingfor 691 of the varianceScans reordered from originalcounterbalanced order forthis display

Maguire et al 65

Behavioral Data

Figure 4a depicts the ground plan of the environmentwith the ve differently shaped rooms (Figure 4b isdescribed under ldquoMethodsrdquo) The average number of dif-ferent rooms visited during each scan of the environ-ment exploration condition was 554 (SD 132)Therefore on average subjects visited all of the areas ofthe environment in their exploration during a scan

Across the four scans of the environment conditionthere was an increase in the number of areas visited withrepeated exposure scan one 45 (SD 105) scan two 55(SD 105) scan three 583 (SD 183) and scan four 633(207) Notably during scans three and four of this con-dition the variance increased Subjectsrsquo reports of explo-ration strategies reveal why this is the casemdashduring laterscans some subjects reported restricting exploration toonly those areas that they were most unsure of whereas

Table 1 Sterotactic Coordinates and Peak Z Scores of the rCBF Increases Associated with Principal Task Comparisons

Talairach coordinates (mm)

Comparison Anatomical regiona x y z z score

1 Environment (with objects) explora-tionmdashrandom colortexture images

L middle occipital gyrus 30 86 12 991

R precuneus 18 70 28 955

R middle occipital gyrus 26 86 8 925

L precuneus 22 64 48 823

R parahippocampal gyrus 22 40 8 765

L cerebellum 42 72 20 717

L fusiform gyrus 28 62 8 703

R cerebellum 26 28 24 282

2a Environment (without objects)explorationmdashexploration of largeopen room



R fusiform gyrus 22 58 8 681

L occipito-temporal gyrus(BA 37)

24 46 12 676

R cuneus 10 98 0 640





2b Environment (without objects)explorationmdashrandom color changes



R cuneus 26 80 20 974

R occipito-temporal region 42 76 0 927





a L = left R = right BA = Brodmannrsquos area


others reported exploring the complete environmentseveral times during later scans Examination of the 24scans (6 subjects times 4 nonlandmark environmentscans) of the environment condition showed that therewere only three instances when subjects (all different)employed a leftright strategy in exploration (ie justkept going systematically left or right at every turn inthe environment) Post-scan testing of ability to way-ndin the environment showed that three subjects per-formed at ceiling level one just below ceiling and twoat chance level In these latter two subjects there wereno identiable features in their exploration strategies or

numbers of rooms visited during scanning to account fortheir poor post-scan performance

PET Data

As in the rst experiment a descriptive data-led eigen-image analysis was initially performed to characterizethe rCBF changes in terms of distributed brain systems(Friston 1994) The principal eigenvector is presentedon Figure 5 It clearly shows positive loading on scanscorresponding to exploration of the environment andnegative loading on those scans corresponding to ran-dom screen color changes This correlated with changesin activity in occipital and occipito-temporal regions forenvironment exploration This distributed neural systemcontrasts particularly with the other explore conditionexploration of the large open room which did not loadsignicantly in either direction The rst eigenvectoraccounts for 77 of the variance in the data and clearlyreects that experimental manipulation by the tasks isthe main contributor to that variance

The rCBF increases associated with the principal taskcomparisons are reported in Table 1 (parts 2a and 2b)and areas of peak activations are superimposed onto atemplate MRI scans in Figure 6 Comparison of the ac-tivity during exploration of the environment with explo-ration of the large open room showed bilateral activityin prestriate regions bilateral occipito-temporal areasthe cerebellum and the precuneus (Figure 6a) The com-parison of the activity during exploration of the environ-ment with random color changes showed a very similarpattern of rCBF changes involving the same regions(Figure 6b) The reverse contrasts were also performedto indicate those areas in which there was a decrease inblood ow during the exploration of the environmentThis showed deactivation bilaterally in frontal areas(peak 40 20 4 Z = 836) and the superior temporalgyrus (peak 54 44 8 Z = 629)

Data were examined to assess any modulation of ac-tivity across the scans of the explore the environmentcondition The only area in which activity signicantlychanged with repetition of the environment task was theright lateral middle temporal gyrus where activity de-creased (50 48 4 Z = 414) The principal task com-parisons were also performed on two subgroups ofsubjects those who performed at ceiling on thepostscan way-nding task (n = 3) and those who per-formed with errors (n = 3) No signicant differencesbetween the two groups emerged

Comparison of the Two Experiments

The principal task comparisons in both experimentalanalyses were compared to ascertain areas of differentialactivation that is [explore the (objects) environment random colortexture images] [explore the (empty)environment random colors] Table 2 (part a) presents

Figure 3 Regions of signicantly greater activation during the ex-ploration of the environment with objects compared to randomcolortexture images Superimposed onto a template MRI scan at thelevel of the peak activation

Maguire et al 67

Figure 4a Aerial view (neverseen by subjects) of theempty environment Close-setlines indicate stairs

Figure 4b Subjectrsquos view of the central room of the environment without objects (actual environment presented in color)


the main ndings from this comparison which showedthat prestriate areas cerebellum precuneus precentralgyrus and the right parahippocampal gyrus were differ-entially active during the task pair subtraction of Experi-ment 1 compared to that of Experiment 2 The maineffects from each experimental analysis were also com-pared to identify areas of common activation betweenthe two pairwise comparisons and peak ndings areshown on Table 2 (part b) Prestriate areas the cuneusfusiform gyrus precuneus and occipito-temporal gyruswere signicantly active during the main task compari-sons in both experiments In summary there were sev-eral brain regions that were signicantly activated inboth experiments some differentially in Experiment 1However the right parahippocampal gyrus was not an

area of common activity across experiments butemerged as active in Experiment 1

DISCUSSION

The principal nding of this study is that exploration ofan environment containing salient objects and textureswas associated with activity in the right parahippocam-pal gyrus whereas exploration of an empty featurelessenvironment activated a network of bilateral occipitalmedial parietal and occipito-temporal regions similar tothe environment with objects but did not activate themedial temporal area We discuss rst those areas com-monly activated in both the environment tasks and then

Figure 5 Principal eigenvec-tor from the data-led eigen-image analysis of Experi-ment 2 (empty) showingclear task effects accountingfor 77 of the variance Scansreordered from original coun-terbalanced order for this dis-play

Maguire et al 69

those regions of signicant rCBF that differed betweenthe two experiments

rCBF Changes Common to Both EnvironmentTasks

The ndings conrm that both environments werebroadly comparable in the network of brain regionsrequired to encode them Given their complex structurecolors and textures and the motion (albeit virtual) ofsubjects through them the associated occipital activa-tions are consistent with previous neuroimaging studiesof the visual system (de Jong Shipp Skidmore Frack-owiak amp Zeki 1994 Shipp Watson Frackowiak amp Zeki1995 Zeki et al 1991) Bilateral activations in the ventraloccipital cortex have also been reported during theviewing of 3-D nonsense objects (Martin et al 1995) andleft middle occipital cortex activation with viewing 3-Dobjects (Malach et al 1995 Price et al 1996) Occipito-temporal and fusiform activations are reported for objectidentication also (Haxby et al 1991 Sergent et al1992) Our prediction of activation of the ventral object

vision pathway (Mishkin et al 1983) associated withobject identication in Experiment 1 is conrmed It isinteresting that the encoding of the featureless environ-ment also gave rise to signicant activity in these regionsCorbetta Miezin Dobmeyer Shulman amp Petersen (1991)showed that focusing attention on the shape of stimuliresults in bilateral activation of the fusiform gyri The veareas within the environment without objects were eacha different geometric shape The fact that all subjectsreported paying attention to shape may explain the ven-tral activations

Increased activity in the medial parietal lobe the pre-cuneus is commonly reported in functional imagingmemory studies (Buckner Raichle Miezin amp Petersen1996 Fletcher Frith Grasby et al 1995 Grasby et al1993) This has been interpreted as being associated withthe retrieval of visual imagery in episodic memoryFletcher Frith Baker et al (1995) conrmed this in astudy where the recall of imageable word pairs but notnonimageable word pairs was associated with signicantactivation of the precuneus Two previous functionalimaging studies of topographical memory encoding Ma-

Figure 6 (a) Regions of signicantly greater activation during the explore the (empty) environment compared to exploring the large openroom Superimposed onto a template MRI scan at the level of the peak activation (b) Regions of signicantly greater activation during the ex-plore the (empty) environment compared to random changing screen colors Superimposed onto a template MRI scan at the level of the peakactivation


guire Frackowiak et al (1996) and Aguirre et al (1996)report the precuneus as active as do we in the presentstudy Activity in this region may relate to the construc-tion of an internal representation of large-scale environ-ments and seems compatible with the role of theprecuneus in imagery Given the exploration inherent inthe environment tasks precuneus activation might alsobe associated with optical ow and locomotion asde Jong et al (1994) report such activations during view-ing of simulated forward motion

While left cerebellar activations have been found withobject recognition (Price et al 1996) the bilateral cere-bellar activity observed in both of the present experi-ments more readily relates to different rates of motor(joystick) movements in the exploration conditions rela-tive to the control tasks Signicant decreases of rCBFwere observed in both experiments in the superior tem-poral gyrus bilaterally during environment explorationMany other PET studies of memory and attention reportdecreases in this region (Grasby et al 1993 Grasbyet al 1994 Jenkins Brooks Nixon Frackowiak amp Pass-ingham 1994 Kapur Friston Young Frith amp Frackowiak1995 Mellet Tzourio Denis amp Mayzoyer 1995 Mosco-vitch et al 1995) Haxby et al (1994) suggest thatattention to visual stimuli may be associated with thesuppression of neural activity in areas processing signalsfrom unattended sensory modalities (eg auditory) andso are reected in blood ow decreases

Differences Between the Activations in the TwoExperiments

In the two experiments we have delineated the basicnetwork for the encoding of large-scale space Efcacyof the encoding process was conrmed by the ndingthat most subjects performed accurately on postscanretrieval tasks In Experiment 1 where subjects exploredan environment containing salient objects the right para-hippocampal gyrus was signicantly activated This re-gion was not activated during exploration of thefeatureless environment Two previous functional imag-ing studies of topographical memory Maguire Frack-owiak et al (1996) and Aguirre et al (1996) presentedenvironments that included salient objects or landmarksThey too found activation of the parahippocampal gyrusOur initial prediction of activity in the medial temporalregion in Experiment 1 is therefore conrmed and is inline with the previous imaging work and with humancases of topographical disorientation following damageto the parahippocampal and medial temporal regions(Habib amp Sirigu 1987 Maguire Burke et al 1996)

Surprisingly the medial temporal region was not acti-vated when subjects explored the environment thatcomprised differently shaped rooms but no salient ob-jects This does not accord with ndings in monkeys inwhich removal of the hippocampal region causesdecits to the memory for places (Angeli et al 1993

Table 2 Comparison of Two Environments Regions of Differential and Common Activation (Peak Voxels)

Talairach Coordinates (mm)

Comparison Anatomical Regiona x y z z score

a Regions of differential activation (en-vironment with objects random tex-turecolor images) (environmentwithout objects random colors)



R precentral gyrus 30 10 48 475





b Regions of common activation(environment with objects randomtexturecolor images) environmentwithout objects random colors)





L occipito-temporal gyrus 22 44 12 926


a L = left R = right

Maguire et al 71

Parkinson et al 1988) It would also seem that despitethe ndings of OrsquoKeefe and Burgess (1996) of geometricdeterminants of place elds in the rat hippocampusshape information from the environment alone does notengage the medial temporal region in humans duringexploration even though it was sufcient to enable way-nding success in the experiment In the real worldhowever large-scale environments typically contain ob-jects or landmarks Environments more complex thanthat of Experiment 2 but with the same lack of environ-mental features and little variation are known to be verydifcult to learn effectively (Evans Fellows Zorn amp Doty1980 Peponis Zimring amp Choi 1990) Therefore whilesubjects could learn a simple environment without land-marks it is likely that this ability would break downunder the complexity of real-world environments andthat the topographical memory system utilizes objectinformation Cognitive models of environmental learningcommonly describe predictable stages in the develop-ment of allocentric representations of large-scale space(Siegal amp White 1975) Typically a signicant role isascribed to distinctive features or landmarks as the initialanchor points of topographical memory formation andthere is empirical support for the importance of land-marks in facilitating spatial and route-learning tasks (Al-len Siegal amp Rosinski 1978 Garling Book amp Ergenzen1982 Presson 1987 Tlauka amp Wilson 1994) Evans Mar-rero and Butler (1981) assessed the sketch maps of newresidents in an urban area over time as familiarity in-creased and found that key landmarks were the compo-nents of initial sketch maps Our current ndings provideevidence that the parahippocampal gyrus provides theneural substrate for landmarkobject-in-place encodingwithin a larger system for topographical learning

The parahippocampal activation cannot be attributedto object processing alone as activity in areas known tobe associated with object vision were found in bothexperiments Tulving Markowitsch Kapur Habib andHoule (1994) and Martin et al (1995) suggest that theright parahippocampal region is involved in novelty en-coding Such an explanation does not t with the presentdata because subjects were familiarized with the land-marks prior to scanning and the degree of novelty asso-ciated with the environment per se was the same inboth experiments The suggestion of Sergent et al (1992)that the right parahippocampal gyrus is a point of con-vergence for perceptual information with episodic mem-ory may be correct but by the same token it does notexplain the absence of parahippocampal gyrus activationin Experiment 2 where the same process would haveoccurred Finally given the nding of Owen et al (1995)of right medial temporal activity associated with theencoding of object location but not location alone onbalance it would seem the parahippocampal activity ismore likely due to the encoding of object location inlarge-scale space

In Experiment 1 rCBF increased in the posterior cin-

gulate cortex during the learning of the environmentSignicant change in the same region was also foundwhen the activity during free exploration strategy wascompared to systematic leftright exploration VogtFinch amp Olson (1992) suggest that the posterior cingu-late may contribute to spatial orientation because of itsanatomical interposition between parietal regions andthe parahippocampal gyrus They propose that the pos-terior cingulate may participate in the transformationfrom a parietal (egocentric) frame of reference to aparahippocampal system based on an allocentric frameof reference The activation of the precuneus posteriorcingulate and parahippocampal gyrus during explora-tion of the environment in Experiment 1 may be evi-dence of this spatial orientation pathway This isparticularly interesting in the comparison between theexploration strategies employed during encodingmdashsys-tematic navigation to either the left or the right canclearly be accomplished in a nonallocentric manner Per-haps the posterior cingulate activity observed only withfree exploration is an index of allocentric processing

In this study parahippocampal gyrus activation wason the right Aguirre et al (1996) also using computer-simulated environments and fMRI found unilateral leftright and bilateral parahippocampal gyrus activationamong their subjects Maguire Frackowiak et al (1996)using real-world stimuli found bilateral parahippocampalactivity Differences in laterality may reect the differen-tial use of disparate strategies in topographic learningsuch as verbal strategies Tlauka and Wilson (1994) foundthe use of a verbal distractor affected route learning insome instances and they concluded that there are manydifferent strategies that humans may make use of whenlearning routes Hermer and Spelke (1994) also suggestthat human adults can use both geometric and non-geometric information to orient themselves

Surprisingly the hippocampus proper was not acti-vated in the present study Maguire Frackowiak et al(1996) with real-world stimuli observed right hippocam-pal activity as well as bilateral parahippocampal activa-tions during topographic learning The question is Howdo the real and simulated environments differ and doesthis relate to hippocampal activity The stimuli of theMaguire Frackowiak et al real-world study unlike thepresent experiments were passive with no interactiveelement subjects watched a lm of navigation througha large-scale environment Their environment was notradially designed or maze-like as in the present study andthe Aguirre et al (1996) study It comprised two longstreets through a town which crossed over at one cen-tral road junction A further difference is that the reallm footage contains a higher density of distinct objectsand features than even the virtual environment used inExperiment 1 It may be that differences such as theserelate to hippocampal activity Further studies areneeded to examine this Virtual environments generallylack the vestibular and kinesthetic stimulation available


when actually navigating in the real world Howevergiven that Maguire Frackowiak et al report hippocam-pus activation with their lm task where these sensoryinputs are also not present the absence of hippocampalactivity in the two present experiments is unlikely to besolely due to a lack of vestibular inputs

Conclusions

We used computer-simulated large-scale environments inorder to examine more precisely the neural correlates oftopographical memory acquisition We determined thatthe parahippocampal gyrus is signicantly involved inthe encoding of an environment within which salientobjects are located a nding that accords with theirdistinct role in cognitive models of environmental learn-ing A featureless large-scale environment with only areashapes as orienting information learned equally well didnot engage the medial temporal region It would seemthat it is the encoding of salient objects and not geomet-ric information in the representation of large-scale spacethat is a critical factor in initiating parahippocampalinvolvement in topographical memory formation in hu-mans

METHODS

Subjects

Eleven right-handed male volunteers aged between 21and 37 years participated in the study None of thesubjects had extensive experience with computer gamesand the associated use of a joystick Five of the volun-teers took part in Experiment 1 and the other six werein Experiment 2 The study involved administration of aneffective dose equivalent of 50-mSv radioactivity Thiswas approved by the Administration of Radioactive Sub-stances Advisory Committee (Department of Health UK)and the local research ethics committee Subjects gaveinformed written consent

Scanning

PET scans were obtained using a SiemensCPS ECATEXACT HR+ (model 962) PET scanner Scanning wasperformed with septa retracted in 3-D mode The eldof view of 155 cm in the axial extent allowed the wholebrain to be studied simultaneously Volunteers receivedan H2

15O intravenous 330-MBq bolus infused over 20 secfollowed by a 20-sec saline ush through a forearmcannula The scan protocol included a delay frame of15-sec to monitor the average radioactivity counts in thescanner The system allows the activation frame to beautomatically triggered dependent on the physiology ofthe individual subject Data were acquired in a 90-secscan frame There were 12 successive administrations ofH2

15O each separated by 8 min The integrated radioac-

tivity counts accumulated over the 90-sec acquisitionperiod corrected for background were used as an indexof regional cerebral blood ow Attenuation correctionwas computed using a transmission scan prior to emis-sion scan acquisition Images were reconstructed into128 acute 128 pixels in 63 planes with an in-plane resolutionof 65 mm

In addition high-resolution magnetic resonance imag-ing (MRI) scans were obtained with a 20 Tesla Visionsystem (Siemens GmbH Erlangen Germany) using a T1-weighted 3-D gradient echo sequence The image dimen-sions were 256 acute 256 acute 256 voxels The voxel size was1 acute 1 acute 3 mm

Experimental Tasks

Experiment 1

There were two experimental tasks each replicated sixtimes The order of tasks was alternated within subjectsand the starting condition alternated between subjectsThe stimuli were presented on a 100-MHz Pentium-based personal computer allowing stimuli to be pre-sented at a frame rate of 35 Hz at high resolutionGraphics were displayed on a 17-in monitor suspendedon a movable gantry above the PET scanning bed withan angle of view of 56deg A commercially available com-puter game (DOOM II copy id Software) was modied toconstruct the virtual reality environment This presentsa color three-dimensional fully textured rst-personview of the simulated environment Subjects controlledtheir movement within the environment with a joystickPrior to the start of scanning acquisition subjects ex-plored a practice environment to become familiar withthe operation of the joystick and the task requirementsThe two conditions were (1) explore the environmentand (2) random colortexture images

Explore the Environment The simulated environmentcomprised a central area off which radiated ve corri-dors At the end of each corridor was a room containingone of ve objects (a aming torch a r tree a candle-stick a burning barrel and a rst-aid kit) There was alsoan object located in the central area The rooms had onlyone exit back into the corridors and each corridor wassufciently curved to prevent one area from being visiblefrom another Figure 1a shows an aerial view of theenvironment Subjects were never shown this aerial per-spective nor were they required to draw sketch mapsduring memory encoding lest this aerial perspectiveshould affect eye-level naturalistic encoding Figure 1bshows a subjectrsquos view of part of the environment (cen-tral area) The corridors and rooms differed in color andtexture Prior to scan acquisition pictures of the velandmarks appeared on the screen for subjects to viewSubjects were instructed to explore the environmentlocating the landmarks and were informed that theywould be tested on their knowledge of the environ-

Maguire et al 73

mentrsquos layout and object locations (see Figure 1c) Theyexplored the same environment during each of the sixscans of the Explore the Environment condition

Random ColorTexture Images (Control) The baselinecondition included for comparison purposes engagedsome of the visual (textures and colors) and motor com-ponents of the explore task In this condition the screenwas lled with successive images similar to the differentcolored textured walls from the environment Some ofthese images stayed stationary others moved either tothe left or the right Subjects were instructed to movethe joystick forward if the image was stationary left if itwas moving left or right if it was moving right

Post-scan Testing Once scanning was nished andwhile still in the scanner subjects were tested on theirmemory for the recently explored environment Theywere instructed to return to various of the objects withinthe environment The test continued for 2 min Afterscanning subjects also drew sketch maps of the environ-ment from memory In addition they gave feedback onhow they had performed the test and strategies em-ployed in exploration during scanning

Experiment 2

There were three experimental tasks each replicatedfour times The order of the experimental tasks wascounterbalanced within and between subjects Thestimulus presentation hardware and software were iden-tical to that used in Experiment 1 Pre-scan practicetiming of tasks data acquisition and analyses were alsothe same The three experimental conditions were (1)explore the environment (2) explore a room (3) andrandom colors

Explore the Environment The simulated environmentcomprised a central octagonal area off which radiatedve corridors At the end of each corridor was a roomeach of the ve rooms being a different shape Figure 4ashows an aerial view of the environment The entrancesto the corridors off the central area appeared identicalIn all cases the entrance led to some ascending stairs ashort landing and then some descending stairs into aroom This prevented one area being viewed from an-other as did the curves in the corridors in Experiment 1There was only one exit back into the corridor from eachroom The rooms and corridors all had the same colorsand textures on their walls oors and ceilings Otherthan the shapes of the rooms there were no distinctivelandmarks present in the environment Figure 4b showsa subjectrsquos view of part of the environment (centraloctagon) Subjects were instructed to explore the envi-ronment and were informed that they would be testedon their knowledge of it They explored the same envi-ronment during each of the four scans of the Explore

the Environment condition For each of the conditionstasks commenced 10 sec prior to the start of scanningacquisition and continued until the end of the 90-secacquisition frame

Explore a Room (Control 1) In this task subjects wererequired to explore a large open circular room of thesame texture and color as those in the larger environ-ment and also without any distinctive features The opti-cal ow and visual demands of the task were very similarto exploring the environment However in this casethere was no exit present and therefore no possibility ofconstructing a spatial map or learning a route

Random Colors (Control 2) A baseline condition wasincluded for comparison purposes that engaged some ofthe visual and motor components of the explore tasksbut without an environmental context In this conditionthe screen changed color after a certain number of leftright and forward joystick moves Subjects were in-structed to move the joystick to keep the screen chang-ing color

Post-scan Testing Once scanning was complete andwhile still in the scanner subjects were tested on theirmemory of the recently explored environment A shapecorresponding to a room shape was indicated on thescreen and subjects had to nd their way to the room ofthat shape in the stimulus environment When leavingthat room another shape appeared and subjects had toproceed to the room of that shape The test continuedfor 2 min Subjects also gave feedback on how they hadperformed the test and strategies employed in explora-tion during scanning

Data Analysis

Images were analyzed using Statistical Parametric Map-ping (SPM95mdashWellcome Department of Cognitive Neu-rology UK) executed in MATLAB (Mathworks IncSherborn MA) This approach combines the general lin-ear model and the theory of Gaussian elds to makestatistical inferences about regional blood ow effects(Friston Frith Liddle amp Frackowiak 1991 FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992) All scans were automat-ically realigned to the rst scan and then normalized intostandard stereotactic space (Talairach amp Tournoux 1988)by matching each scan to a reference or template thatalready conforms to the standard space therefore allow-ing pixel-by-pixel averaging across subjects The struc-tural MRI scans were normalized into the same space toallow for the superimposition of PET activations onto anaveraged structural image Images were smoothed usingan isotropic Gaussian kernel of 16 mm (FWHM) to opti-mize the signal-to-noise ratio and to adjust for intersub-ject differences in gyral anatomy Global variance


between conditions was removed using analysis of co-variance (ANCOVA) For reach pixel in stereotacticspace condition-specic adjusted rCBF values with anassociated adjusted error variance were generated Areasof signicant change in brain activity were then deter-mined using appropriately weighted contrasts betweenthe task-specic scans and using the t statistic The re-sulting set of t values constituted the statistical paramet-ric map (SPM) Signicance levels were set at P lt 005(corrected for multiple comparisons)

Acknowledgments

Support from The Wellcome Trust is gratefully acknowledgedWe thank Clive Parker and Tom Hartley for technical help NBurgess is supported by a Royal Society University ResearchFellowship

Reprint requests should be sent to Eleanor Maguire WellcomeDepartment of Cognitive Neurology Institute of Neurology12 Queen Square London WC1N 3BG UK or via e-mailemaguirelionuclacuk

REFERENCES

Aguirre G K Detre J A Alsop D C amp DrsquoEsposito M(1996) The parahippocampus subserves topographicallearning in man Cerebral Cortex 6 823ndash829

Allen G L Siegal A W amp Rosinski R R (1978) The role ofperceptual context in structuring spatial knowledge Jour-nal of Experimental Psychology Human Learning andMemory 4 617ndash630

Angeli S J Murray E A amp Mishkin M (1993) Hippocampec-tomised monkeys can remember one place but not twoNeuropsychologia 31 1021ndash1030

Buckner R L Raichle M E Miezin F M amp Petersen S E(1996) Medial parietal (precuneus) activation during epi-sodic memory retrieval One area that is involved and onethat isnrsquot Neuroimage 3 S533

Corbetta M Miezin F M Dobmeyer S Shulman G L amp Pe-tersen S E (1991) Selective and divided attention duringvisual discriminations of shape color and speed Func-tional anatomy by positron emission tomography Journalof Neuroscience 11 2383ndash2402

de Jong B M Shipp S Skidmore B Frackowiak R S J ampZeki S (1994) The cerebral activity related to the visualperception of forward motion in depth Brain 117 1039ndash1054

De Renzi E (1985) Disorders of spatial orientation In J A MFrederiks (Ed) Handbook of clinical neurology (vol 1pp 405ndash421) Amsterdam Elsevier

Evans G W Fellows J Zorn M amp Doty K (1980) Cognitivemapping and architecture Journal of Applied Psychology65 474ndash478

Evans G W Marrero D G amp Butler P A (1981) Environ-mental learning and cognitive mapping Environment andBehavior 13 83ndash104

Feigenbaum J D Polkey C E amp Morris R G (1996)Decits in spatial working memory after unilateral tempo-ral lobectomy in man Neuropsychologia 34 163ndash176

Feigenbaum J amp Rolls E T (1991) Allocentric and egocen-tric spatial information processing in the hippocampal for-mation of the behaving primate Psychobiology 19 21ndash40

Fletcher P C Frith C D Baker S C Shallice T Frackowiak

R S J amp Dolan R J (1995) The mindrsquos eyemdashprecuneusactivation in memory-related imagery Neuroimage 2 195ndash200

Fletcher P C Frith C D Grasby P M Shallice T Frack-owiak R S J amp Dolan R J (1995) Brain systems for en-coding and retrieval of auditory-verbal memory Brain118 401ndash416

Friston K (1994) Functional and effective connectivity inneuroimaging A synthesis Human Brain Mapping 2 56ndash78

Friston K J Frith C D Liddle P F amp Frackowiak R S J(1991) Comparing functional (PET) images The assess-ment of signicant change Journal of Cerebral BloodFlow and Metabolism 11 690ndash699

Friston K J Holmes A Worsley K J Poline J B FrithC D amp Frackowiak R S J (1995) Statistical parametricmaps in functional imaging A general linear approach Hu-man Brain Mapping 2 189ndash210

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the signicance of focal ac-tivations using their spatial extent Human Brain Map-ping 1 214ndash220

Garling T Book A amp Ergenzen N (1982) Memory for thespatial layout of the physical environment Differentialrates of acquisition of different types of information Scan-dinavian Journal of Psychology 23 23ndash35

Goldstein L H Canavan A G M amp Polkey C E (1989) Cog-nitive mapping after unilateral temporal lobectomyNeuropsychologia 27 167ndash177

Grasby P M Frith C D Friston K J Bench C FrackowiakR S J amp Dolan R J (1993) Functional mapping of brainareas implicated in auditory-verbal memory functionBrain 116 1ndash20

Grasby P M Frith C D Friston K J Simpson J FletcherP C Frackowiak R S J amp Dolan R J (1994) A gradedtask approach to the functional mapping of brain areas im-plicated in auditory-verbal memory Brain 117 1271ndash1282

Habib M amp Sirigu A (1987) Pure topographical disorienta-tion A denition and anatomical basis Cortex 23 73ndash85

Haxby J V Grady C L Horwitz B Ungerleider L GMishkin M Carson R E Herscovitch P Shapiro M B ampRapoport S I (1991) Dissociation of object and spatial vi-sion processing pathways in human extrastriate cortexProceedings of the National Academy of Sciences USA88 1621ndash1625

Haxby J V Horwitz B Ungerleider L G Maisog J MPietrini P amp Grady C L (1994) The functional organisa-tion of human extrastriate cortex A PET-rCBF study of se-lective attention to faces and location Journal ofNeuroscience 14 6336ndash6353

Hermer L amp Spelke E S (1994) A geometric process forspatial reorientation in young children Nature 370 57ndash59

Jenkins I H Brooks D J Nixon P D Frackowiak R S J ampPassingham R E (1994) Motor sequence learning A studywith positron emission tomography Journal of Neurosci-ence 14 3775ndash3790

Kapur N Friston K J Young A Frith C D amp FrackowiakR S J (1995) Activation of human hippocampal forma-tion during memory for faces A PET study Cortex 31 99ndash108

Landis T Cummings J L Benson D F and Palmer E P(1986) Loss of topographical familiarity An environmentalagnosia Archives of Neurology 43 132ndash136

Maguire E A Burke T Phillips J amp Staunton H (1996)Topographical disorientation following unilateral temporallobe lesions in humans Neuropsychologia 34 993ndash1001

Maguire et al 75

Maguire E A Frackowiak R S J amp Frith C D (1996) Learn-ing to nd your waymdasha role for the human hippocampalregion Proceedings of the Royal Society of London Se-ries B Biological Sciences 263 1745ndash1750

Malach R Reppas J B Benson R R Kwong K K JiangH Kennedy W A Ledden P J Brady T J Rosen B R andTootell R B (1995) Object-related activity revealed byfunctional magnetic resonance imaging in human occipitalcortex Proceedings of the National Academy of SciencesUSA 92 8135ndash8139

Martin A Wiggs C Ungerleider L amp Haxby J (1995) Neu-ral correlates of category specic knowledge Nature379 649ndash652

Mellet E Tzourio N Denis M amp Mayzoyer B (1995) A posi-tron emission tomography study of visual and mental spa-tial exploration Journal of Cognitive Neuroscience 7433ndash445

Mishkin M Ungerleider L G amp Macko K A (1983) Objectvision and spatial vision Two cortical pathways Trends inthe Neurosciences 6 414ndash417

Moscovitch M Kapur S Kohler S amp Houle S (1995) Dis-tinct neural correlates of visual long-term memory for spa-tial location and object identity A positron emissiontomography study in humans Proceedings of the Na-tional Academy of Sciences USA 92 3721ndash3725

OrsquoKeefe J amp Burgess N (1996) Geometric determinants ofthe place elds of hippocampal neurons Nature 381425ndash428

OrsquoKeefe J amp Dostrovsky J (1971) The hippocampus as aspatial map Preliminary evidence from unit activity in thefreely-moving rat Brain Research 34 171ndash175

OrsquoKeefe J amp Nadel L (1978) The hippocampus as a cogni-tive map Oxford Clarendon Press

OrsquoMara S M Rolls E T Berthoz A amp Kesner R P (1994)Neurons responding to whole-body motion in the primatehippocampus Journal of Neuroscience 14 6511ndash6523

Owen A M Milner B Petrides M amp Evans A C (1995)The role of the right hippocampal region in the encodingand recall of object-location A PET study Society for Neu-roscience 21 1211

Parkinson J K Murray E A amp Mishkin M (1988) A selec-tive mnemonic role for the hippocampus in monkeysMemory for the location of objects Journal of Neurosci-ence 8 4159ndash4167

Peponis J Zimring C amp Choi Y K (1990) Finding the build-ing in waynding Environment and Behavior 22 555ndash590

Pigott S amp Milner B (1993) Memory for different aspectsof complex visual scenes after unilateral temporal- orfrontal-lobe resection Neuropsychologia 31 1ndash15

Presson C C (1987) The development of landmarks in spa-tial memory The role of differential experience Journalof Experimental Child Psychology 44 317ndash334

Price C J Moore C J Humphreys H W FrackowiakR S J amp Friston K J (1996) The neural regions sustain-ing object recognition and naming Proceedings of theRoyal Society London Series B263 1501ndash1507

Rolls E T Cahusac P M B Feigenbaum J D amp Miyashita Y(1993) Responses of single neurons in the hippocampusof the macaque related to recognition memory Experimen-tal Brain Research 93 299ndash306

Rolls E T Robertson R G amp Georges-Franccedilois P (1995)The representation of space in the primate hippocampusSociety for Neuroscience Abstracts 21 1492

Sergent J Ohta S amp MacDonald B (1992) Functionalneuroanatomy of face and object processing Brain 11515ndash36

Shipp S Watson J G D Frackowiak R S J amp Zeki S(1995) Retinopic maps in human prestriate visual cortexThe demarcation of areas V2 and V3 Neuroimage 2 125ndash132

Siegal A W amp White S H (1975) The development of spa-tial representation of large-scale environments In H WReese (Ed) Advances in child development and behav-ior (Vol 10 pp 9ndash55) New York Academic Press

Smith M L amp Milner B (1981) The role of the right hippo-campus in the recall of spatial location Neuropsycholo-gia 19 781ndash793

Smith M L amp Milner B (1989) Right hippocampal impair-ment in the recall of spatial location Encoding decit orrapid forgetting Neuropsychologia 27 71ndash81

Talairach J amp Tournoux P (1988) Co-planar stereotactic at-las of the human brain Stuttgart Thieme

Tlauka M amp Wilson P N (1994) The effect of landmarks onroute-learning in a computer-simulated environment Jour-nal of Environmental Psychology 14 305ndash313

Tulving E Markowitsch H J Kapur S Habib R amp HouleS (1994) Novelty encoding networks in the human brainpositron emission tomography data Neuroreport 5 2525ndash2528

Vogt B A Finch D M amp Olson C R (1992) Functional het-erogeneity in cingulate cortex The anterior executive andposterior evaluative regions Cerebral Cortex 2 435ndash443

Worsley K J Evans A C Marrett S amp Neelin P (1992) Athree-dimensional statistical analysis for rCBF activationstudies in human brain Journal of Cerebral Blood Flowand Metabolism 12 900ndash918

Zeki S Watson J D G Lueck C J Friston K J Kennard Camp Frackowiak R S J (1991) A direct demonstration offunctional specialization in human visual cortex Journalof Neuroscience 11 641ndash649

Zola-Morgan S amp Squire L (1985) Mesial temporal lesionsin monkeys impair memory on a variety of tasks sensitiveto human amnesia Behavioral Neuroscience 99 22ndash34


ing temporal lobectomy patients rst-person perspectivelm footage of navigation through an urban area andexamining learning and memory along a range of pa-rameters Decits in topographical memory were iden-tied in patients with unilateral medial temporal-lobelesions on both the left and the right where generalneurological and neuropsychological functioning was in-tact These ndings correspond to previously reportedcases of topographic difculties after damage encom-passing the parahippocampal region (Habib amp Sirigu1987) and similar impairments in cases with bilateral andunilateral lesions involving the temporal lobe (De Renzi1985 Landis Cummings Benson amp Palmer 1986)

Recent functional imaging work has attempted to pro-vide further insights into the precise neural substrates ofspatial memory in humans Owen Milner Petrides andEvans (1995) using positron emission tomography (PET)found activation of the caudal region of the right medialtemporal region associated with the encoding of objectlocations from an array on a computer screen but notwith the encoding of location alone Recall of objectlocation was associated with activation of the right para-hippocampal gyrus Moscovitch Kapur Kohler amp Houle(1995) in contrast found activation of the supramarginalgyrus to be associated with the recall of object locationHowever in the latter case there were only three objectlocations per trial whereas the Owen study had eightper trial Thus differences in memory load andor spatialarray complexity may be the basis of these differentactivations Neither the Owen nor Moscovitch studiescapture the allocentric frame of reference that is thebasis of topographic representations of large-scale spaceGiven the restrictive environment of brain scanners ex-amining topographical memory or way-nding necessi-tates the use of novel stimuli Maguire Frackowiak andFrith (1996) used PET to measure regional cerebralblood ow (rCBF) while normal subjects memorizedlm footage depicting either navigation in an urban areaor nonnavigation events in a similar environment Onlythe viewing of the navigation lm footage resulted infocal and signicantly increased activation of the para-hippocampal cortex and hippocampus on the right andthe parahippocampal cortex on the left Aguirre DetreAlsop and DrsquoEsposito (1996) report similar parahippo-campus activations with a computerized topographicallearning task using functional magnetic resonance imag-ing (fMRI) It would seem therefore from human lesionand functional imaging work that the parahippocampalgyrus bilaterally is critical for topographical memoryformation whereas the functional signicance of thehuman hippocampus proper is currently less-well spe-cied

In the present PET study we used computer-simulatedrst-person virtual reality environments to simulate navi-gation in large-scale space Elements of these environ-ments were manipulated in order to examine moreprecisely the neural correlates of topographical memory

acquisition This approach has the added advantage ofaffording more naturalistic self-directed exploration onthe part of subjects In the rst experiment the virtualenvironment included specic objects as well as variedtextures and colors In the monkey two distinct andfunctionally specialized cortical pathways have beenidentied for object processing an occipito-temporalpathway for the recognition of objects and an occipito-parietal pathway for processing spatial relations amongobjects (Mishkin Ungerleider amp Macko 1983) In PETstudies there has been some support for homologousprocessing pathways in humans (Haxby et al 1991 Mar-tin Wiggs Ungerleider amp Haxby 1995 Price MooreHumphreys Frackowiak amp Friston 1996) However ob-ject recognition studies generally examine objects lo-cated in egocentric space In particular this does notadequately capture the spatial essence of objects inlarge-scale space that must be located in an allocentricframe of reference The neural correlates of object en-coding in the context of topographical memory forma-tion remain unspecied Based on previous studies wepredicted that encoding of the environment with ob-jects would activate areas known to be involved inobject identication (Haxby et al 1991 Sergent Ohta ampMacDonald 1992) and the topographical memory en-coding would activate the medial temporal region in linewith Maguire Frackowiak et al (1996) and Aguirre et al(1996)

All previous topographical memory studies have usedenvironments that had objects present In a secondexperiment in this study the layout of the virtual en-vironment while broadly similar to that in the rst ex-periment was effectively free of salient objects andtextures Differences in the shape of rooms were theonly distinguishing features that enabled subjects to en-code meaningful environmental information The pur-pose of using this environment was to extend theinvestigation of the topographical memory acquisitionprocess beyond previous studies by examining its neuralsubstrates where environmental inputs were more spe-cically identiable This is the rst instance in functionalimaging where topographical learning based only ongeometric information has been examined Given theOwen et al (1995) nding of activation in the rightcaudal medial temporal region associated with objectlocation on a computer screen but not location aloneone might expect there to be no medial temporal activ-ity associated with the encoding of the featureless envi-ronment However the Parkinson et al (1988) and Angeliet al (1993) reports of decits in hippocampectomisedmonkeys in both place-only and object-in-place spatialdelayed responses suggest that the medial temporal re-gion may be implicated in the spatial representationirrespective of the presence of objects Hermer andSpelke (1994) found that young children reorient them-selves in accord with geometric or shape informationfrom the environment and OrsquoKeefe and Burgess (1996)




RESULTS



Behavioral Data



PET Data



Maguire et al 63













Maguire et al 65

Behavioral Data




















24 46 12 676

R cuneus 10 98 0 640








R cuneus 26 80 20 974










PET Data







Maguire et al 67






DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75


































RESULTS



Behavioral Data



PET Data



Maguire et al 63













Maguire et al 65

Behavioral Data




















24 46 12 676

R cuneus 10 98 0 640








R cuneus 26 80 20 974










PET Data







Maguire et al 67






DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75












































Maguire et al 65

Behavioral Data




















24 46 12 676

R cuneus 10 98 0 640








R cuneus 26 80 20 974










PET Data







Maguire et al 67






DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75








































Maguire et al 65

Behavioral Data




















24 46 12 676

R cuneus 10 98 0 640








R cuneus 26 80 20 974










PET Data







Maguire et al 67






DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75
































Behavioral Data




















24 46 12 676

R cuneus 10 98 0 640








R cuneus 26 80 20 974










PET Data







Maguire et al 67






DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75


































PET Data







Maguire et al 67






DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75





































DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75


































DISCUSSION



Maguire et al 69
































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75































































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75
























































Maguire et al 71









Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75








































Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75

































Conclusions


METHODS

Subjects


Scanning






Experimental Tasks

Experiment 1



Maguire et al 73




Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75



































Experiment 2







Data Analysis




Acknowledgments



REFERENCES































Maguire et al 75

































Acknowledgments



REFERENCES































Maguire et al 75































































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Knowing where things are: Parahippocampal involvement in encoding object locations in virtual...

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