supplied as Poewrpoitn files, coped into document [1, 2, 3, 4, 5,6,7, 9, 11,] Scanned & edited [8, 10, 12] COGNITIVE NEUROPSYCHOLOGY, 2001, 18 (6), 481–508

NEUROPSYCHOLOGICAL EVIDENCE FOR A TOPOGRAPHICAL LEARNING MECHANISM IN PARAHIPPOCAMPAL CORTEX

Russell Epstein Medical Research Council Cognition and Brain Sciences Unit, Cambridge, UK and MIT Department of Brain and Cognitive Sciences, Cambridge, USA Edgar A. DeYoe Medical College of Wisconsin, Milwaukee, USA Daniel Z. Press Beth Israel Deaconess Medical Center, Boston, USA Allyson C. Rosen Stanford University, Stanford, USA Nancy Kanwisher MIT Department of Brain and Cognitive Sciences, Cambridge, USA

The ParahippocampalPlace Area (PPA;Epstein &Kanwisher, 1998)is a region within posterior parahippocampal cortexthat respondsselectively to visual stimuli that conveyinformation about the layoutof localspace. Here wedescribe twopatients whosuffered damage tothe PPAafter vascular inci - dents.Both subsequently exhibited memory problems fortopographical materials and were unable to navigate unassisted in unfamiliar environments. Performance onacontinuous n -back visualmemory test wassignificantly lowerfor novel scene -likestimuli than fornovel object -likestimuli. In contrast, performance wasnormal ona famouslandmark recognition taskand ontwo perceptual tasksthat required on-line analysisof scene geometry. Bothpatients were able toproduce accurate maps of premorbidly learned placesbut were unable toproduce accurate maps ofnew places.These results con - verge with previous neuroimaging workto demonstrate that the PPA(1)is selectively involved in pro - cessing information about the geometry ofsurrounding space,and (2)may playa more critical rolein the encoding ofthis information into memory than in the initial perceptual processing,recognition, or recall of this information.

Requests forreprints shouldbe addressedto RussellEpstein, MRCCognition &Brain Sciences Unit, 15Chaucer Road,Cam - bridge CB2 2EF,UK (Tel:+44 (0) 1223 -355-294,ext. 800; Fax: +44 (0)1223 -359-062;Email: russell.epstein@mrc -cbu.cam.ac.uk). Wethank Damian Stanleyand Alison Harrisfor assistance with these experiments, Stephan Heckersand Facundo Manes for anatomical advice,Kim Graham forcomments on the manuscript, TomHammeke foradvice about neuropsychologicaltests, Matthew Brett forassistance with MRInormalisation, and MarvinChun, Frances Wang,and Liz Spelkefor helpful discussions. In addition, we wouldalso like to expressour thanks to GRand COfortheir cheerfuland enthusiastic participation in this research.This research was supported byNIMH postdoctoral fellowship MH11459 to RE,NEIand NIMHgrants EY10244and MH51358to EAD, and NIMH grant MH56037 to NK.

Ó 2001 Psychology Press Ltd 481 http://www.tandf.co.uk/journals/pp/02643294.html DOI:10.1080/02643290042000215 EPSTEINET AL.

INTRODUCTION McCarthy, Evans, &Hodges,1996; Whiteley & Warrington, 1978). Allmobile organisms must solvethe fundamental Based oncomprehensive review of the topo - problemof navigation. One way togain insight into graphical disorientationliterature, Aguirre and thecognitive and neural mechanisms underlying D’Esposito(1999) argued that thelingual - navigation is toinvestigate thefunctional organisa - parahippocampal regionis oneof several areas that tionof thebrain areas involved.Research onani - are critically involvedin navigation. Damage tothis mals and humans has suggestedthat anumber of regionoften results in an inability touse salient top - regionsplay arole,including theparietal lobes ographical features such as landscapes and build - (Stark,Coslett, & Saffran, 1996),retrosplenial cor - ings toorient oneself (“ landmark agnosia,”e.g., tex(Chen, Lin,Green, Barnes, &McNaughton, Landis etal.,1986; Pallis, 1955) or in amoregen - 1994),hippocampus (Maguire etal.,1998; O’ Keefe eralinability tolearn new topographical informa - &Nadel,1978), and parahippocampal cortex tion(“ anterograde disorientation,” e.g., Habib & (Aguirre,Detre, Alsop, & D’Esposito,1996; Sirigu,1987, patients 1and 2).In arecentstudy of Bohbotet al., 1998). Here we focus onpara - 127patients withfocal lesions,Barrash, Damasio, hippocampalcortex. We describetwo patients who Adolphs,and Tranel(2000) observed that patients suffereddamage tothis regionof cortex after vascu - withdamage tothis regionalmost always displayed lar incidents.Both subsequently developedsevere severeimpairment ona real -worldroute learning deficits in thetopographical domain, which we task. Furthermore,Bohbot et al.(1998) found that defineas thedomain of information relevantto patients withright -hemisphereparahippocampal spatial navigation. cortexlesions were impaired at ahuman analogue Previous reportsin theneuropsychological liter - oftheMorris water maze task in whichthey were ature have describedpatients with“ topographical requiredto remember the location of ahiddenfloor disorientation,”who are unable tosuccessfully find platformwithin aroom(a deficitnot found in theirway throughlocomotor space but donot patients whosedamage was restrictedto the hippo - exhibitgeneral cognitive or memory impairments campus proper). (seeAguirre & D’Esposito,1999, for review). The Neuroimaging studies have alsoimplicated the nature ofthespecific problemvaries frompatient to lingual-parahippocampal regionin navigation. patient.For example,some patients showan inabil - Severalstudies have examinedbrain activity innor - ity tounderstand spatial relationships betweendif - malsubjects during performanceof a number of ferentlocations (Levine, Warach, &Farah, 1985, navigational tasks, including navigation througha patient 2),whereas others are unable torecognise virtual realityenvironment (Aguirre etal., 1996), navigationally relevantstimuli such as landmarks watching videotapesdepicting navigation through but can accurately describeroutes between the arealenvironment (Maguire, Frackowiak, &Frith, places theycannot identify(Pallis, 1955).Patients 1997),and mentallyimagining navigation through alsodiffer in theirrelative ability tohandle novel vs. arealenvironment (Ghaem etal.,1997; Maguire et familiar topographicalinformation. Some are able al.,1998). All ofthesestudies foundgreater activa - tonavigate throughfamiliar environmentsor recall tionin theparahippocampal region(and sometimes oldtopographical information but cannot learn othermedial temporal regions as well,Ghaem et novelenvironments (Habib &Sirigu,1987, al.,1997; Maguire etal.,1997, 1998) when the nav - patients 1and 2;Ross, 1980;Teng &Squire,1999), igation task was comparedto a lessnavigationally whereasothers are impairedat bothlearning ofnew demanding control task. materials and recognition/recallof old materials What roledoes parahippocampal cortexplay in (Habib &Sirigu,1987, patients 3and 4;Incisa thesenavigational tasks? In earlierwork, we dellaRocchetta, Cipolotti, & Warrington, 1996; addressedthis question by using fMRI toexamine Landis, Cummings, Benson,& Palmer,1986; neural activity in parahippocampal cortexand other

482 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING brain regionswhile subjects vieweda widevariety of infants (Hermer& Spelke,1994, 1996; Hermer - visual stimuli (Epstein &Kanwisher,1998). We Vazquez, Spelke,& Katsnelson,1999) that suggest foundthat aregionabutting thecollateral sulcus that information about thegeometry of surround - near theparahippocampal -lingual boundary ing space—the “ lay oftheland” — plays aprivileged respondedsignificantly morestrongly when sub - role in orientation and navigation. jectsviewed navigationally relevantstimuli such as What specific cognitivetask doesthe PPA per - streetscenes, landscapes, orbuildings than when form?Given thefact that landmarkagnosia often theyviewed other kinds ofvisual stimuli such as results fromparahippocampal -lingual damage faces, objects,or scrambled scenes 1.This response (Landis etal., 1986), one might hypothesise that was foundeven when subjects simply watchedthe theprimary roleof thePPA is placerecognition: stimuli passively and werenot required to perform identification offamiliar locationsbased ontheir any navigational task. Wenamed this regionthe appearance and/orgeometric structure. If so,one “parahippocampal placearea,” or PPA, because it mightexpect the PPA tobesensitive tothe novelty/ respondedstrongly to depictions of places. The familiarity ofthe place depicted in thestimulus. PPAappears tooverlap with the regions activated However,we foundthat thePPA respondsjust as in previous neuroimaging studies ofnavigation stronglyto photographs of unfamiliar places (i.e., (e.g., Aguirre et al., 1996). places thesubjects had nevervisited) as itdoes to Acritical determinantof PPA activation photographsof familiar places (Epstein etal., 1999, appears tobethe presence in thestimulus ofinfor - Expt.1). In contrast, thePPA is sensitive tothe mation about theshape orlayoutof theimmediate novelty/familiarity ofthestimulus itself,respond - environment.The PPA respondsno more strongly ing morestrongly to new photographs than topho - tophotographs of roomsfilled with furniture and tographs viewedmany timespreviously even when objectsthan itdoes to photographs of the same allthe photographs depict unfamiliar places roomsempty of all objects (i.e., just bare walls).It (Epstein etal.,1999, Expt. 4). From theseresults, alsoresponds much morestrongly to “ scenes”made weinferred that thePPA is moreinvolved in outof Legoblocks (which have ageometricstruc - encodinga representationof the spatial structure of turesimilar toa roomor streetscene) than itdoes to thecurrent scenethan in relatingthat sceneto one’ s objectsmade out of the same Legomaterials storedcognitive map ofthe environment as a (Epstein,Harris, Stanley,& Kanwisher,1999). whole.However, our data didnot allow us todeter - Thus, thePPA is sensitive tothepresence of a spe - minewhether the PPA activation reflectspercep - cific kindof geometricorganisation in thestimulus tual encoding, memory encoding, or both. evenif thestimulus doesnot depict a realplace in Thepurpose of thepresent report was tomore theworld. In particular, itresponds more strongly preciselydetermine the function ofthe PPA. To todepictions of surfaces that in somesense this end,we tested the ability ofour two patients to “enclose”the observer and definea space within perceive,learn, and recognisea variety ofvisual whichone can act (i.e.,the walls of aroomor the materials. Wepredictedthat thepatients wouldbe sideof thedistant hill)than todepictionsof surfaces moreimpaired at processing scene -likestimuli (i.e., that defineobjects that theobserver can act upon. stimuli that depictspaces that onecan navigate Theseresults are generallyconsistent withbehav - throughor act within) than object -likestimuli. By iouralresults fromrats (Cheng, 1986;Gallistel, using severaldifferent kinds oftests,we aimed to 1990;Margules &Gallistel,1988) and human determinewhether any such selectiveimpairment

1 Although fullscenes activate the PPAmorestrongly than doany other kind ofvisualstimulus, we havealso observed higher activity in the PPAwhen subjects view buildings than when they view otherkinds ofobjects (Epstein et al.,1999), consistent with Aguirre, Zarahn,and D’Esposito’s (1998)finding ofasignificant response to buildings in an adjoining and possiblyoverlapping region of the anterior lingual gyrus.

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 483 EPSTEINET AL. was in theperceptual, recognition, or memory dividedinto four subsections. First, wepresent a domain.To anticipate, wedidfind evidencefor a generaloverview of the case histories.Second, we deficitfor visual materials that conveyedinforma - reportthe results ofsomead hoctests that givea tionabout theshape ofsurrounding space. This generalindication ofthepatient’ s navigational abil - deficitmanifested itselfduring amemoryencoding ities.Third, we discuss othercognitive abilities, testbut notduring perceptualtests orarecognition including face recognitionand episodicmemory. test.Thus, ourdata suggest that thePPA is neces - Fourth,we report the results ofabattery offormal sary forthe encoding of spatial layoutinformation neuropsychologicaltests performedon thepatients. intomemory, but may notbe necessary formany Table 1summarises relevantobserved and self - aspects ofthe initial perceptualanalysis, recogni - reportedbehaviour, and Table 2summarises the tion,or recallof this information.We argue that the results of the neuropsychological tests. PPAmay bea learning mechanism specifically ded - icatedto encoding topographical materials into Overview memory. Case 1: GR GR2 is a right-handedmale with 18 years ofeduca - CASE DESCRIPTIONS AND tion.He was 60years oldat thetime of testing. NEUROPSYCHOLOGICAL TESTING Two-and-a-half years priorto testing, he suffered a right occipital -temporalstroke during cardiac Inthis section,we presentthe case historiesof the surgery. Asecondstroke affecting theleft occipital - twopatients inorderto provide a generalcontext temporalregion occurred a weeklater. These forthe more specific experimentaltests reported strokesleft him with a number ofdeficits, including in theExperimental Investigations section.The limitationof his peripheralvision (left patients werechosen for investigation because clin - hemianopsia, right upperquadrantanopsia), ical MRIs indicatedthat theyhad suffered damage dyschromatopsia (details reportedin Beauchamp tothe parahippocampal region.This sectionis etal.,2000), and topographicaldisorientation. We

Table 1. Summary of observed and self -reported behaviour GR CO Real-world topographicalUnable to recognise 7/14 newly learned MIT landmarks,Unable to learn 3 -room videogame learning despite extensive training regime. environment. Unable to find way back to lab unassisted, despite Able to learn a simple route out of extended experience with environment. building after many visits. Map drawing Could not draw map of lab; maps of other newly learnedMap of lab was sketchy, but not entirely environments were inaccurate. inaccurate. Drew accurate map of premorbid environment Drew accurate map of premorbid (former home). environment (current/former home). Scene perception Reports difficulty understanding the globality of complexDoes not report a perceptual deficit. scenes. Face recognition Some prosopagnosia. Severe prosopagnosia. Episodic memory Largely intact, though some difficulties were reported.Moderate difficulties were reported.

Can follow the plot of a movie or novel and report Reports some difficulty following the previous day’s activities. plot of a book. Accurately reported contents of previous day’s newspaper.

2 GR’s true initials areKG (c.f.,Beauchamp, Haxby,Rosen, & DeYoe,2000), and CO’s true initials areKC. We use GRand CO here to avoid confusion between the two patients.

484 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

Table 2. Summary of neuropsychological tests (% indicates percentile scores) GR CO —————————— ———————————– IQ 122 (93%, WAIS -R) 134 (99%, WAIS -III) WMS-III Logical memory 25% immediate recall 27% immediate recall 50% delayed recall 48% delayed recall(WMS -R) Face memory 9% immediate recall 16% immediate recall 16% delayed recall 9% delayed recall

Family pictures 2% immediate recall <1% immediate recall 5% delayed recall <1% delayed recall

Rey Auditory Verbal 63% immediate recall 45% immediate recall Learning test 14% after interference list <1% after interference list 16% delayed recall 3% delayed recall

Warrington Recognition 50% words Memory tests 29% scenes <5% faces 7/24 Spatial Recall 66% immediate recall 2% delayed recall

Benton Face Recognition 42% <1%

Memory span Digits: 99% forward 99% backward Spatial: 37% forward 50% backward

Boston Naming test Ceiling Ceiling testedhim over a periodof 5 days in August 1998, injury, hemoved to a neighbourhoodwith many with3 days offollow -up testing 3weekslater, and 1 similar-lookinghouses. He reportedthat in order day ofadditional tests in May 1999.During this tofind his newhouse after awalkto a marketsix to time,he was alertand cooperative.Emotional sevenblocks away, hehad torely on streetsigns to affect and language use was normal.He interacted guidehim to thecorrect block, and thenexamine normallyin nonclinical social situations, and his each houseon the block in detailuntil he could conversation was appropriateand varied.He recognisesome feature that distinguished his home rememberedthe events of previous days and uniquely.Subsequently, GR and his wifemoved to recounted them accurately. adifferenthouse in adifferentcountry. He reported Incontrast tothis high levelof non - that forthe first 6monthsafter themove, his new topographicalfunctioning, GRdemonstrateda homewas likea “hauntedhouse” for him insofar as dramatic inability toorient himself in space. For hewas unable tolearn his way around it.For exam - example,even after severaldays oftesting,he never ple,he would repeatedly forget that thebedroom learnedthe relative locations of thedifferent rooms had abalcony, and hewouldbe surprised by this fact ofthe lab. According to both GR and his wife,this everytime he rediscovered it. After several months, inability tolearn new topographical information however,he was ableto learn the topography of the was typical ofhis experiencesince his strokes,as he housesufficiently wellto navigate throughit (but frequentlygets lostin his dailylife. Soon after his see below).

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 485 EPSTEINET AL.

Case 2: CO UnlikeGR, CO was ableto learn a certain CO is a left-handedmale with 20 years ofeduca - amount oftopographical information. For exam - tion.He was 60years oldat thetime of testing.Two ple,he soon learned the location of the rooms in the years priorto testing hesuffered a right posterior lab and wouldtravel between them unassisted. cerebralartery stroke.He first noticedon aweek - Afterhis first visit tothe lab heneeded to be guided endthat his vision appearedblurred on the left and allthe way back tothe subway station, but after sev - that hehad atendencyto bump intoobjects on this eralvisits hecould find his way outof thebuilding side.On Mondaymorning, he was ableto success - and tothe subway onhis ownas longas hewas first fullynegotiate the route to his workplace,a tripthat guidedto theelevators. (It shouldbe noted, how - involveda bus ridefollowed by twosubways and ever,that thebuilding is onthesame blockas the thena shuttleto his officebuilding. However, once subway station. Furthermore,he still needed to be heentered the building hefound himself com - directedto the elevators even though our building pletelydisoriented, unsure ofits layoutand where has arelativelysimple floor plan.) Thus, theamount his officewas located.Interestingly, the company oftopographicalinformation hecan learnis limited heworked for had moveda fewweeks earlier. but not zero. Althoughhe had managed toarrive at this new CO’s language and reasoning skillsappear tobe building (which was ablockaway fromthe previous normal,and his conversation is appropriateand location),he became lostupon entering it. His varied.In addition to his topographicaldifficulties, neurologicexam revealeda lefthomonymous healso has limitations ofhis peripheralvision on hemianopia but noevidence of neglect on aletter the left side. cancellationtask oron sensory testing.Investiga - tions revealedan ischaemic strokewith haemor - Navigational abilities rhagic transformation in theright occipitaland mesialtemporal lobe. On magnetic resonance Inaddition to the experiments reported in the angiography hehad achronic leftcarotid occlusion, ExperimentalInvestigations sectionof this paper, amildright carotidstenosis, and bilateralvertebral wealsoperformed a number ofad hoctests ofGR artery stenoses.Since then, he has suffered from and CO’snavigational abilities. Althoughthese severetopographical disorientation, primarily in tests wereinformal, we describe them here to pro - new environments. videa generalsketch of thenature ofGRand CO’s COreportsthat hecan recognisebuildings that impairments. werefamiliar tohim before the stroke. He can also formmental images ofwell -knownlandmarks such Real-world topographical learning as theEmpire State Building and theBoston Over thecourse of severaldays, wetook GR and his Public Gardens, and ofthe house he lived in as a wifeon threewalks around theMIT campus, which child.When asked to imagine standing in front of neitherhad visitedpreviously. Each walkfollowed theMassachusetts StateHouse (a locationwell exactlythe same path.At severalplaces in thewalk, knownto him from years ofliving in Boston),he wewouldstop and pointout different buildings and accurately describedthe surrounding buildings and landmarks,tell them something about each oneand theirlocations. However, he reportsthat whenhe ask themto remember their appearance forlater looksat aplacethat he’s encounteredpost -stroke, testing.Immediately after thecompletion of the allhe gets is afeelingof familiarity that doesnot thirdwalk, both GR and his wifeseparately per - allowhim to determine where the place is orwhen formeda forced -choicerecognition test in which hesaw it.He also reportsan inability tounderstand theysaw photographsof 14 landmarks (mostly howvarious landmarks relateto each otherin buildings) fromthe walk and 14novel landmarks large-scale space. Despitethis difficulty,he can (from anotherpart ofthe MIT campus that they followa map and frequentlyrides the Boston had notvisited) and wererequired to report subway alone. whetherthey had seeneach oneor not. GR’ s

486 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING performancewas 7/14correcthits forthe familiar simplicity ofthis artificial environment,CO’ s com - landmarks and 13/14correct rejections for the plete inability to learn it is striking. unfamiliar landmarks. Incontrast, his wife obtaineda perfectscore on this test.Given the Map drawing extensivenature ofthetraining regime,GR’ s score Afterseveral days oftesting,we askedboth GR and stronglysuggests an impairment in learning the his wifeto sit at differenttables and independently appearance ofnewreal -worldplaces. Interestingly, sketch(1) theshape ofFlorida,(2) abicycle,(3) a severalof theseven familiar landmarks that hegot floorplan oftheir hotel room in Boston,(4) afloor right had an obvious distinctive feature that had plan ofthefirst floorof the house they had beenliv - beenexplicitly pointed out to him. For example, ing in forthe last 8months (allpost -stroke),(5) a onebuilding had adistinctive clocktower, and floorplan ofthemain roomof thelab, and (6) a anotherone was an unusual triangular shape.Thus, floorplan ofthe house they lived in 10years ago GRwas occasionally ableto use distinct visual (pre-stroke).GR drewthe map ofFloridaand the features toidentify places eventhough he was bicycleperfectly. His plan ofthe hotel room was unable torecognise them holistically— acommon notably differentfrom the one drawn by his wife— pattern among topographicaldisorientation forexample, he reported that therewas onlyone patients. bedwhen in fact therewere two, and heplaced the GRdidnot appear tohave any obvious problems bedon thewrong side of theroom (Figure 1a). His in understanding thespatial structure ofhis imme - plan ofthefirst floorofhis current housewas some - diateenvironment. When given afloorplan ofthe what betterbut was notvery detailed and included building at MITin whichhe was being tested,he somemajor errors.For example,he wrongly was ableto successfully followa routemarked on reportedthat therewas nobathroom on this floor theplan. However, when the plan was takenaway, (Figure 1b).He was unable toproduce any floor hehad great difficulty finding his way back tothe plan ofthemain roomof thelab, leaving this page lab eventhough he had morethan 30min experi - blank.When his wifereminded him that this was encewith the environment and his starting position theroom in whichhe had just spent an hourreading was lessthan 30feet from the goal (Figure 2).In thenewspaper and in whichwe had allhad break - fact, theroute he took resembled a randomwalk. At fast in that morning,he repliedthat hedidn’t know onepoint, he walked right past his destination what roomshe was talkingabout (although he withoutrecognising it,and onlyknew for sure that appearedto remember these events). In contrast to hewas in theright placewhen he identifiedhis wife this near totalinability toproduceaccurate maps of in theroom. Thus, his on -lineappreciation ofthe newenvironments, GR producedan accurate map layoutof immediately visible space appears tobe ofthehouse he livedin priorto his injury (Figure intact, but hecannot find his ownway without 1c).He reported that his memoryof this housewas assistance. “allthere” and hecouldimagine walkingaround in Wewere unable toperformthe MIT landmark it.When asked to produce a perspectiveof aroom recognitiontest on CO because hesufferedfrom a whenhe was in it,he did so withease, and hewas medicalproblem that madeit difficult forhim to also ableto create an accurate floorplan ofthe walkaround campus. In lieuof this, we triedto see room. whetherhe couldlearn a simplevideo game envi - In contrast, COfoundit very difficult topro - ronmentconsisting ofthree connected rooms. ducea floorplan ofthelab bothwhen he was in it Afterabout 30min experiencenavigating through and whenhe was takento another room and asked this environment(via button presses) hewas asked torecall it. However, although the maps hepro - tosketch a map ofit.He declinedto do so, stating ducedwere quite impoverished, they were not that itwas beyondhis abilities.When asked how entirelyinaccurate, demonstrating someability to many roomsthere were, he repliedthat hedid not encodetopographical information. This contrasts know,but that therewere at least10. Given the withGR’ s absolute inability torecall anything

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 487 EPSTEINET AL. p F r i i g o u r G H H r t e o o R i s 1 G t . e R w l ’ s F r i f i o l e n o o j o u r m r p y l . a i n n s d B r a o w s n t o b y n G R a n d h i s w i f e o f ( a ) t h e i r h o t e l G C H r o u R i o s m r r w e i n n i f B t e o h s t o o n m , ( b e ) t h e i r c u r r e n t h o u s e , w h i c h t h e y h a d m o v e d t G F o H o s R u i s r b m s e w q e u i f e r e n h t t o o m G R e ’ s i n j u r y , ( c ) t h e h o u s e t h e y l i v e d i n

488 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

problem,or a memoryproblem (see discussion). COdidnot complain of asimilar deficit.GR was an accomplishedartist priorto his injury, producing paintings ofstriking complexity.Tragically, he reportsthat hecannot nowappreciate his own paintings.

Other cognitive abilities Face recognition GRalso reportedsome difficulties withface recog - nition.On his secondvisit, weexamined his ability tolearn new faces by having himperform a forced - choicerecognition test on sevenfamiliar and seven Figure 2. Floor plan of the building at MIT in which GR was tested. Corridors are highlighted in grey. GR was asked to find the unfamiliar faces. Thefamiliar faces werepersonnel main room of the lab (marked G on the map). Starting location fromthe lab withwhom he had at that pointhad a (marked S) was a point approximately 30 feet down the hall. GR’s gooddeal of experience,spanning at least3 days. route is marked by arrows. GR found this task very difficult, and Allthe people in thephotographs had atowel only knew for certain that he had reached his goal when he caught wrappedaround theirhead in orderto minimise the sight of his wife through the glass door of the lab. In contrast, he was able to follow a route marked on a plan of the same floor use ofhair as anonfacial cue.Despite the difficulty without any problem or hesitation. ofthis task, hecorrectly identified 6/ 7familiar faces, and madeno false alarms. Surprisingly,the about themain roomof thelab oncehe had leftit. oneface that hedid miss was thefirst author ofthis COwas alsoable to draw adetailedfloor plan ofthe paper,with whom he at that pointhad had consid - apartment hewas living in at thetime (and had erableexperience. GR alsoperformed normally on livedin for20 years). Severalmonths after hehad adifficult famous face recognitiontest (see Experi - movedfrom this apartment, weaskedhim to draw ment4, following)and ontheBenton Face Recog - such afloorplan again, and heproducedone that nition test(see following). Thus, hehas some was substantially thesame as thefirst (Figure 3). ability torecognise faces. Consistent withthis, GR Thus, theirmap drawing performanceindicates reportsthat he can remembera smallnumber of that GRand COare primarily impairedat sketch - faces, but that hequickly“ losestrack” if hehas to ing places experiencedafter theirstrokes, but are remember too many. unimpaired at sketchingplaces experiencedbefore COalsoappears tosuffer fromsome theirstrokes. This pattern isindicative ofdeficits in prosopagnosia, as evidencedby his lowperfor - encoding but not recall. mance onthe Benton Face Recognitiontest (see following;see also Experiment4). Interestingly, he Scene perception doesnot complain of face recognitiondifficulties, Asnotedearlier, GR can navigate withthe aid ofa but ratherattributes his inability torecognise peo - floorplan, suggesting that his perceptualabilities ple to a lack of interest in their appearance. are largelyintact. Interestingly,however, he reports that he does have aperceptualdeficit, which he Episodic memory describes as an inability tounderstand scenes when Atfirst glance,GR’ s episodicmemory appeared to theyare toocomplex. For example,he reportsthat belargely intact. Asmentioned,he couldrecall the heoften has troubleusing maps because they eventsof theprevious day accurately. Furthermore, usually are toobusy withdetails. It is unclear hereports that hecan followthe plot of a movie whetherthis apparent perceptualproblem is aresult withoutany difficulty.However, both he and his ofhis fieldcut, some other separate perceptual wifereport that hedoeshave someproblems with

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 489 EPSTEINET AL.

CO, home, Feb 99

CO,(former) home, June 99

Figure 3. Two floor plans drawn by CO of the apartment he lived in for over 20 years. The first plan was drawn when CO still lived in the apartment; the second was drawn several months later when he had moved out. Note that the two plans correspond very well. CO reported that it was quite easy to produce these floor plans. episodicmemory. For example,he stated that he whichmay manifest itselfas an inability tosepa - rememberedvery little about atripto Italy they had ratelyremember successive eventsthat are noteasily takenseveral months previously. His wifereports distinguishable from each other. that hehas great difficulty keepingtrack oftime: COalso reportssome problems with his epi - For example,before their trip to Boston, he repeat - sodicmemory. He relies on lists toremember edlyasked her what day theywere supposed to leave appointments,stating “if Ididn’t have alist,I’ d and seemedunable toencode this information.We probably forgetwhy I walkedin thedoor here.” observeda similar phenomenonduring testing: Despitethis claim,he has nevermissed an appoint - During thetests that requiredrepetition of the ment,nor is heeverconfused about thepurpose of same procedureseveral times, he sometimes thetesting appointments.He can accurately report seemedunable toclearly remember how many theday ofthe week. He remembers the experi - timeshe had repeatedthe procedure. Thus, hedoes mentersclearly from appointment to appointment, appear tohave asubtleepisodic memory deficit, as wellas thedetails of the various experiments

490 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING whenthey are repeatedacross appointments.When and delayedrecall (16th percentile; SS =85). On a queriedabout his episodicmemory difficulties, CO recognitiontest of the items of thelist, he success - reportedthat hewill usually rememberan eventif fullyrecognised all 15, but made8 false alarms. Per - heis remindedof it,but that hehas difficulty spon - formance onthe 7/ 24Spatial Recall Test (Rao, taneously regeneratingevents. Interestingly, he Hammeke,McQuillen, Khatri, & Lloyd,1984), reportsthat evenwhen he is remindedof an event whichrequired him to remember seven locations on and remembersit, he cannot remember“ whereit a 6 ×4checkerboard,was 66thpercentile (SS =106) was orwhen it was.” When he reads,he finds itdif - forimmediate and 2ndpercentile (SS = 69) for ficult tofollow a story if it skips around.However, delayedrecall. Performance on the Benton Face whenqueried, he was ableto accurately reportwhat Recognitiontest was normal(42nd percentile). he had read in the newspaper the previous day. Performanceon the Boston Naming Test was at ceiling,indicating that language abilities were intact. Thus, GRexhibits someimpairment on Formal neuropsychological tests tasks that requiredelayed recall of visual informa - Formal neuropsychologicaltesting was performed tion (WMS-IIIFace Memorysubtest) orverbal onGR in September1998 and onCOin December information that is notorganised in termsof astory 1998.Test performances werecompared to age - orplot (Rey AVLT),and is clearlyimpaired on matched peers 3. tasks that requireddelayed recall of spatial informa - GRexhibitedmild to moderate impairment in tion(7/ 24SpatialRecall Test) orstimulus location memoryrelative to what wouldbe predicted for his (WMS-IIIFamily Pictures subtest). Incontrast, intellect(WAIS -RFullScale IQ =122;93rd per - his ability torecall organised verbal information centile;superior range) and levelof education. (WMS-IIILogicalMemory subtest) appears tobe Thesememory problems were more apparent on intact. visual than onverbal memorytests. On atestof Aswith GR, CO’smemoryperformance was memoryfor conceptually organised textpassages generallybelow what wouldbe expected based on (WechslerMemory Scale Logical Memory intellect(WAIS -IIIFullScale IQ =134;99th per - [WMS-III];Wechsler, 1997b) his performance centile;very superior range) and educationlevel. was average forboth immediate (LM I =25th per- Alsolike GR, therewas someevidence that visual centile;standard scoreSS = 90)and delayedrecall memoryproblems were more pronounced than ver - (LM II =50thpercentile, SS =100).In contrast, his bal memoryproblems. Memory for text passages scoreon theWMS -IIIFace Memorysubtest was in (WMS-RLogicalMemory) was average forboth thelow average range forboth immediate (9th per - immediate(27th percentile; SS = 91)and delayed centile; SS =80)and delayedrecall (16th percentile; recall(48th percentile; SS =99).In contrast, perfor - SS =85).Onatestof memoryfor scenes (WMS -III mance onthe WMS -IIIFaces subtest was low Family Pictures subtest), immediaterecall was defi - average forboth immediate (16th percentile; SS = cient(2nd percentile; SS = 69)and delayedrecall 85)and delayedrecall (9th percentile; SS =80), and was borderlineimpaired (5th percentile; SS = 76). performanceon the Family Pictures subtest was GRalso had difficulty learning wordlists: on the deficient (< 1stpercentile; SS < 62)forboth imme - Rey AuditoryVerbal Learning Test (Spreen& diateand delayedrecall. On theWarrington Rec - Strauss, 1998)his immediaterecall was average ognitionMemory Tests (RMT), hescoredin the (63rdpercentile; SS = 105)but after theinterfer - average range forwords (50th percentile; SS =100) encelist his performancefell to the low average and scenes (Warrington Topographical Recogni - range forboth immediate (14th percentile; SS =84) tionMemory Test; 29th percentile; SS =92), and in

3 The formalneuropsychological testing reportedin this section was performedprior to the beginning ofour combined investigation ofGRand CO(i.e.,prior to the main experimental investigations ofthis paper).Consequently, GRand COwere not tested on exactly the same battery of tests.

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 491 EPSTEINET AL. thedeficient range ( < 5thpercentile; SS < 75) for right hemisphere,the hippocampus is spared,but faces. Thelow score for faces onthis testas wellas thereis damage tothe posterior end of the the WMS-IIImay reflectprosopagnosia rather parahippocampal gyrus near theparahippocampal - than amemoryproblem, as hescoredin thedefi - lingual boundary. Moreposteriorly, the lesioned cientrange ( <1stpercentile; SS < 62)on theBenton area extendsalong the collateral sulcus toinclude Face Recognitiontest. Verbal list learning (Rey significant portionsof theinferior lingual gyrus and AVLT) was average onimmediaterecall (45th per - themedial fusiform gyrus, as wellas mostof the centile; SS = 98),but after hearing an interference medial occipital lobe below the calcarine fissure. listperformance fell to the deficient level (0/ 15 COhas aright -hemisphereoccipital -temporal wordsrecalled) for both immediate and delayed lesion.Right posteriorhippocampus and para - recall.On arecognitiontest for these words, he hippocampalgyrus are severelyaffected. More recognised11/ 15and madeone false alarm (39th posteriorly,the damage coverslarge portions of the percentile,SS =96).There was alargediscrepancy inferiorlingual and medialfusiform gyri,as wellas ontests ofmemory span, whichmay indicate a substantial portionsof the medial occipital lobe declinein spatial memory:digit span was superior including mostof right calcarine cortex.In addi - (9+forward and 7backwards; both99th percentile) tion,diffuse foci ofincreased signal onT -2 but spatial span was onlyaverage (5forward and 5 weightedimages was presentin periventricular backward; 37thand 50thpercentiles respectively). whitematter in thecorona radiata and centrum Language abilities wereintact (Boston Naming semiovalewith a lacunar infarct ofthe right Test performancewas at ceiling).Thus, likeGR, putamen.There was also moderatedegree of dif - COshows someimpairment at recallof visual fuse involutionalchanges withincreased ventricular information (WMS -IIIFace Memorysubtest) and size,particularly notablein theright temporalhorn verbal information that is notorganised intoa nar - with ex vacuo dilitation. rative (Rey AVLT),and clearimpairment at tasks Thestructural MRIs suggestedthat thePPA that requirerecall of stimulus location(Family Pic - was severelyif notcompletely damaged in both tures subtests ofWMS -III).In contrast, his ability hemispheresfor GR, and intheright hemisphere torecall organised verbal information (WMS -R forCO. In orderto confirm this forGR, weused a Logical Memory subtest) is more preserved. high-field 3-Tmagnet toperform a functional scan in whichhe viewed scenes, faces, and objectsin the same blockedfMRI design that wehave usedto MRI RESULTS localisethe PPA in allour previous experiments (seeEpstein et al., 1999, for details; Epstein & In orderto determine the extent of their lesions, Kanwisher,1998). A Kolomogorov -Smirnovtest structural MRI images weretaken of both subjects. found no voxelsin theparahippocampal regionthat Delineationof the lesions was based eitheron fit ourpreviously established criterion for inclusion spoiledGRASS coronal images at 1.1mmthick - in thePPA (i.e.,greater response to scenes than to ness (GR) oranatomical T -1weightedMPRAGE faces and objectsat auncorrectedsignificance level MRI sequences yielding1.25 mm thick coronal of p< .0001).This resultcontrasts sharply withthe images (CO). Theanterior -posteriorextent of the pattern seenin over95% of (mostly young ormid - lesions was verified on axial images. dle-aged) normalsubjects, in whoma largeacti - GRhas bilateraloccipital -temporallesions vatedregion can beidentified in bothleft and right (Figure 4).In theleft hemisphere, the posterior parahippocampal cortexusing this comparison (see parahippocampal gyrus (including para - Figure 5).A similar testwas usedto identify voxels hippocampalcortex) is severelydamaged, with only that respondedsignificantly moreto faces than to minimal injury tothe most caudal aspect ofthehip - objects.This comparison revealeda regionof face - pocampus. Thereis also moderatedamage tothe selectivevoxels in theright fusiform gyrus consis - medialfusiform and inferiorlingual gyri.In the tentwith the location of the Fusiform Face Area

492 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

GR

CO

Figure 4. Structural MRIs of GR and CO showing the extent of the damaged region (marked as white). Images have been normalised using SPM99 and a cost function masking algorithm (provided by Matthew Brett) into standard stereotactic space (Talairach & Tournoux, 1988) using the Montreal Neurological Institute template (Evans et al., 1993). Numbers indicate y -Talairach coordinate for each coronal slice; corresponding slice planes are also indicated on the sagittal image.

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 493 EPSTEINET AL.

FFA PPA wouldhave moredifficulty withscene -likestimuli (i.e.,stimuli that conveyinformation about the geometryof aspace onecan navigate throughor act within) than withobject -likestimuli. Such a deficit couldaccount forat leastsome of the problems GR GR and CO encounter in real -world navigation. Beyonddetermining the kind ofvisual material that gets processedin parahippocampal cortex,we also wantedto determinethe nature ofthe process - ing that takes placeon that material.In particular, wewantedto determine if parahippocampal cortex NK is involvedin perceptualencoding , memory encoding , or recognition .Asdiscussed earlier(Introduction), ourfMRI results providedsome evidence against placerecognition as thesole function ofthePPA, but didnot allow us todistinguish betweenpercep - Figure 5. Top row shows a single slice from a functional MRI tual and mnemonicencoding. Experiments 1 and 2 scan performed on GR. Bottom row shows results from a normal examinethe role of parahippocampal cortexin per - subject (NK) for comparison. Voxels that responded more to faces ceptualencoding, Experiment 3 examines its rolein than objects (left column) or more to scenes than faces and objects (right column) in a Kolomogorov -Smirnov test are highlighted by mnemonicencoding, and Experiment4 examines white arrows. GR has a functioning face area (FFA), but there is its role in place recognition. no evidence of a place area (PPA). Experiment 1: Two dot task (FFA) commonlyseen in normalsubjects - (Kanwisher, McDermott,& Chun, 1997).Thus, Thefirst hypothesiswe examined was that theMRI was sensitive enoughto detectfunctional parahippocampal cortexplays arolein perceiving differences:an FFA was found,but noPPA. When theshape ofthelocal environment. In ourprevious combinedwith the anatomical results,this strongly fMRI work,we observed that thePPA responds suggests that GR has no PPA. much morestrongly during sceneviewing than dur - Because ofsafety concerns (presenceof afemo - ing objector face viewing,even when subjects do ral artery aneurysm clip),we didnot perform a simi - nothing morethan watch thescenes passively with - lar high-fieldfunctional MRIofCO. However,as outperforming any othertask. This suggestedthat Figure 4demonstrates,CO clearlyhas damage to sceneperception alone may besufficient toactivate theparahippocampal -lingual regionin theright thePPA. Previous reportshave indicatedthat dam - hemisphere. age toparahippocampal cortexand othermedial temporalregions leads to problems with memory ratherthan perception(Bohbot et al., 1998; EXPERIMENTAL INVESTIGATIONS Maguire,Burke, Philips, & Staunton,1996; Pigott &Milner,1993). However, all of these previous Inthis section,we reportthe results offour experi - results wereobtained on patients whohad unilat - ments designedto probethe consequences ofdam - erallesions. GR has abilateraloccipital -temporal age tothe lingual -parahippocampal regionin lesion,including cleardamage toparahippocampal generaland thePPA in particular. Our primary cortexin bothhemispheres; furthermore, he reports concernin theseexperiments was totest GR and somekind of perceptualdeficit. We hypothesised CO’s ability toperceive, remember, and recognise that this deficitmight involve difficulty perceiving differentkinds ofvisual material.Based onour pre - orinterpreting the geometry of scenes and other vious fMRI work,we predictedthat GRand CO stimuli with a similar geometric structure.

494 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

Inthis experiment,subjects viewedeither object Method shapes orspatial layouts.Stimuli consisted of Testing forall experiments was doneon a black-and-whitephotographs of real -worldstimuli Macintosh computer.The experiment consisted of (emptyrooms vs. commonobjects) orabstract 80trials (20of each stimulus type,randomly inter - stimuli madeout of Legoblocks (Lego “ scenes”vs. mixed).Subjects began each trial by pressing the Lego“ objects”). Thesestimuli have beenpreviously space bar. Ablack -and-whitephotograph from one shown todifferentiallyactivate thePPA in normal ofthe four stimulus categories(see earlier) then subjects (Epstein etal., 1999; Epstein & appearedon the screen, with two red dots on it.The Kanwisher,1998). Two red dots were superim - task was todetermine which of the two red dots posedon each photograph(Figure 6).The task was indicatedthe closer part ofthe scene or object. toreport which of the two red dots was overthe Subjects pressedthe “ f”keyif theleftmost red dot closerpart ofthe object or scene. This task was was closest,and the“ j”key if therightmost dot designedto have nomemory component (apart was closest.They were instructed torespond as fromremembering the instructions), but torequire quicklyas possiblewithout making errors.Stimuli accurate 3D perception of objects and scenes. remainedon thescreen until a responsewas made. If GRorCOhave difficulty perceivingor inter - Thestimulus setwas constructedso that each pretingthe spatial layoutof scenes, then we pre - emptyroom was matchedto a commonobject that dictedthey would do worse when the stimuli are had reddots in theexact same location,and each emptyrooms or Lego scenes than whenthey are Legolayout was similarly matchedto a Legoobject. real-worldor Lego objects. Note that thecritical Thus, thelocations of thered dots were counterbal - comparison is betweenthe Lego scenes and the anced across sceneand objectstimuli, controlling Legoobjects, as thesestimuli are madeof thesame for any effects of visual field cuts. materials and differprimarily in theirsurface geometry. Results and discussion Results forGR and COand four elderlynormal subjects are shownin Table 3.BothGR and CO coulddo this task withoutdifficulty, and theirper - formance was near ceiling.There was noevidence that theyhad any moretrouble with the empty roomsor Lego scenes than withthe real or Lego objects.Reaction timeswere slightly longer for GR and COthan fornormal subjects, as onewould expectgiven theirvisual fielddeficits; however, this

Table 3. Experiment 1 (two -dot) results (SD in parenthesis)

GR CO Normals

Proportion correct: Object 0.950.80 0.93 Lego object 1.000.95 0.98 Empty room 1.001.00 0.99 Lego room 0.951.00 0.96

Mean RT: Object 24352932 2161 (980) Lego object 20523245 2029 (921) Figure 6. The four kinds of stimuli used in Experiment 1. Top Empty room 27442291 1788 (959) left: lego layouts, top right: real world layouts (empty rooms), - Lego room 19042281 1630 (1127) bottom left: lego objects, bottom right: real -world objects.

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 495 EPSTEINET AL. differencedid not appear tobe significant. Impor - memoryfor 10 s, and thenalign it(presumably tantly,there was littleevidence that GRorCOtook using mentalrotation), to the second object or longerto maketheir perceptual judgements for the scene. realor Legoscenes than forthe real or Legoobjects. Thus, contrary toourinitial hypothesis,this experi - Method mentfound no clear evidence for selective impair - Theexperiment consisted of two parts, each with ment in the perception of scene -like stimuli. 40trials. Inthe first part,the stimuli wereblack and whitephotographs of objects made out of Lego blocks.In thesecond part, the stimuli werephoto - Experiment 2: Different views matching - graphs of“scenes”made out of Lego blocks, which task weredesigned to have ageometricstructure similar Theprevious experimentdemonstrated that GR to real-worldplaces such as aroomor acity street. and COcan extract information about theper - Subjects began each trial by pressing thespace ceiveddistances betweenthemselves and thesur - bar. Aphotographof a Legoobject or scene faces ofan objector scene. Thus, in at leastone appearedon thescreen for 3 s, followedby a10 -s sense,their perception of these surfaces is pre - blank interval.A secondphotograph then appeared served.However, this doesnot mean that theirabil - depictingeither (1) thesame objector sceneas the ity torepresentthe layout of asceneis unimpaired. first photographshown from a differentviewing The two-dottask requires on -linecomparison of angle(offset approximately35 degrees),or (2) adif - twosurfaces inegocentriccoordinates. GR and CO ferentobject or scene.Subjects wereinstructed to wouldbe able to performthis task evenif theycould press the“ j”key if thetwo photographs depicted the not(1) representmore than twosurfaces at atime, same objector sceneand the“ f”keyif theydid not. (2) representsurfaces in otherthan strictly egocen - Theywere told to takeas much timeas theyneeded tric coordinates,or (3) sustain surface representa - tomake a decisionbut noextra time.The second tions forlonger than thetime it takes tomake a photographremained on thescreen until a response comparison. Ithas beensuggested that theparietal was made.Half thetrials were“ same”trials and half lobesare involvedin on -lineprocessing ofsurface were “different” trials. geometryin egocentriccoordinates (Milner & Goodale,1995); thus it ispossiblethat theparietal Results and discussion lobes(which are intact in GRand CO)may besuf - Figure 8shows results forGR and COas wellas for ficient toperform the two -dottask evenin the six elderlynormal controls. GR’ sand CO’s perfor - absence ofmore durable or complexsurface repre - mance was comparable tothat ofthe normal con - sentations in parahippocampal cortex. trols.Furthermore, GR and COperformedjust as InExperiment 2, we examine GR and CO’s wellwhen the stimuli wereLego scenes as when ability tocreate and sustain arepresentationof the theywere Lego objects. These results are unlikelyto geometryof an objector scene -likelayout. The task reflecta ceilingeffect as performancefor both was toviewa photographof aLegoobject or Lego patients and controlswas around 80%correct. scene,hold it in memoryfor 10 s, and thendeter - Thus, bothpatients appear tobe able to form a rep - minewhether a secondobject or scenewas thesame resentationof the geometry of both scenes and as thefirst. In“same”trials thesecond photograph objectswhich they can sustain in short -term depictedthe same sceneor objectdepicted from a memory. differentviewing angle.In “different”trials thesec - ondphotograph depicted a differentscene or object Experiment 3: N back recognition memory chosento be similar tothe first one(Figure 7). - task Thus, in orderto successfully performthis task, subjects had toform a representationof the surfaces Theprevious experimentfailed to find any impair - ofthe object or scene,sustain this representationin mentin GRand CO’s ability toform a representa -

496 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

(a) Lego layout version

3 s 10 s OR

(b) Lego object version

3 s 10 s OR

Figure 7. Stimuli and procedure for Experiment 2. (a) In the Lego layout version, subjects see a Lego layout for 3 s followed by a blank screen for 10 s. A second layout then appears which is either the same layout as the first one but seen from a different angle, or a different layout. (b) The Lego object version is the same but with object stimuli. tionof the geometry of a sceneor object and shouldnote that subjects in this experimentwere maintain itfor 10 s in theabsence oftheoriginal freeto devote all their effort and attentionin the10 - stimulus. Notonly does this resultsuggest that per - secondblank interval tomaintaining amemoryof ceptionof scene -likestimuli is intact in these thestimulus. Thus, itis possiblethat GRand CO patients, itfurther suggests that someshort -term can use rehearsalmechanisms tomaintain thestim - memoryfunctions are intact as well.However, we ulus in short -termmemory during theblank inter -

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 497 EPSTEINET AL.

reportedwhether they had seenit before in the experimentor not. In differentruns in theexperi - ment,the stimuli wereblack -and-white photo- graphs of(1) Legoscenes, (2) Legoobjects, (3) real - worldlandscapes, (4) novelobjects made out of Sculpeyclay, (5) unfamiliar houses,(6) unfamiliar faces, as wellas (7) linedrawings ofnonsense objects,and (8) pronounceablepseudowords (Fig - ure9). Thus, wewere able to test GR and CO’srec - ognitionmemory for different kinds of materials at differenttime intervals in aparadigm in whichthe presenceof intervening itemsbetween the two Figure 8. Results of Experiment 2. Performance over “same” appearances ofeach stimulus maderehearsal diffi - trials and “different” trials is averaged together. Error bars show cult.Note that because noneof thespecific stimuli 1 SD. usedin this experimentwere familiar in advance, this task didnot require an episodicmemory com - val,but are unable toform a moredurable memory ponentand couldbe done on thebasis ofpure visual trace forthe stimulus. This possibility was testedin familiarity with the particular visual stimulus. thecurrent experiment,which was designedto Althoughmany differentstimulus classes were examineGR and CO’sability tolearn new visual testedin this experiment,the critical comparison is information. betweenthe Lego layouts and Legoobjects, Wedevised a continuous n -back recognition because theseare best matchedwith regard to memorytest in whichsubjects vieweda sequenceof materials and differprimarily in theirgeometric originallynovel stimuli, some of which were structure (seeIntroduction). We predicted that if repeatedwithin thesequence at intervals of1,3,or GRand COshoweda memorydeficit for this task, 5intervening images. For each stimulus, subjects itwould be greater for the Lego layouts than forthe

Figure 9. Stimuli for Experiment 3. Top row: Lego layouts, real -world scenes, houses. Bottom row: Lego objects, clay objects, nonsense objects, faces. In an eighth condition (not shown) subjects viewed pronounceable nonwords such as “wilch” or “thipper.”

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Legoobjects. In addition,a deficitfor materials layouts and Legoobjects, so presentationtime was that conveyinformation about thelayout of sur - extendedto 2 sforthese categories in his first test - rounding space mightalso beapparent whenGR ing session. Allnormalsubjects weretested at these and COare testedon more realistic stimuli.If so, presentationrates (2s forLego layouts and objects, onewould expect them to do poorlyon theland - 1sforother stimuli). In CO’s secondtesting scapes, but relativelywell on the clay objects,line session, presentationtime was lengthenedto 3 sfor drawings ofnonsense objects,faces, and allstimulus categoriesto ensure that any deficits pseudowords. foundwere memory deficits ratherthan problems with the nonmemory aspects of the task. Method For each subject, acompleteexperimental session Results and discussion consistedof being run onceon each ofthe eight Results fromGR, CO, and 10elderly normal con - stimulus classes. Each run consistedof 90trials; in trolsare shownin Figure 10and Table 4.Figure 10a each trial astimulus was presentedand subjects shows results fromthe main comparison between reportedwhether or not they had seenit beforein Legolayouts and Legoobjects. Both normal sub - therun (or indeed,ever) by pressing the“ j”key if jectsand patients performednear ceilingfor both theyhad orthe “ f”keyif theyhad not.Each stimu - Legolayouts and Legoobjects at 1 -back lus was onthescreen for either 1, 2, or3s(seefol - interstimulus intervals, verifying that GRand CO lowing),and appearedpromptly after thekeypress couldsuccessfully perceivethe pictures as theywere reportfor the previous trial.Individual stimuli being presented.In contrast, therewas astriking appearedeither once (14 stimuli), twice(30 stim - differencebetween the two patients and thenormal uli),or four times(4 stimuli) within agiven run. Of subjects at 5 -back intervals.Whereas normals did thestimuli that werepresented twice, 10 were onaverage somewhatbetter on Legolayouts than repeatedimmediately (1 -back), 10were repeated Legoobjects, both GR and COshowedthe oppo - witha lag oftwointervening items(3 -back), and 10 sitepattern, doing much worseon Lego layouts wererepeated with a lag offour intervening items than Legoobjects. The 3 -back conditionshowed a (5-back). Inorderto ensure that between -subject mixedpattern: Whereas GRdidbetter on Lego differencesin performancewere not due to stimulus objectsthan Legolayouts inthis condition(similar differences,the same stimuli wereassigned tothe tohis performanceat 5 -back intervals), COdid same conditionseach timethe experiment was run. betteron Legolayouts than Legoobjects. CO’ s low GRperformedthe experiment twice: once in performanceon Legoobjects in the3 -back condi- August 1998,and again 9months later.Because of tionappears tobe an anomaly,as it is much lower acomputererror, he was onlytested on six ofthe than his performancefor comparable stimuli in the eightcategories (all except Lego layouts and Lego 1-back and 5-back conditions. objects) at thelater date. CO was also testedtwice: Figure 10bshows thedifference in performance oncein February 1999,and again 6monthslater. betweenLego layouts and Legoobjects for the Reportedresults forGR and COare theaverage of critical 1-back and 5-back intervals. At5 -back theirtwo testing sessions. Normalsubjects were intervals, COwas significantly impairedcompared onlytested once. Stimulus presentation time was 1s tothe normal subjects (z = –2.50),whereas in GR’s first testing session. In pilottesting, CO GR’s impairment felljust shortof significance (z = foundthis toofast forthe critical categoriesof Lego –1.75)4.

4 In fact, these valuesmay underestimate GRand CO’s relativeimpairment forLego layouts. In the 5 -back condition, 4ofthe 10 normalsubjects hadperfect performanceon the Legolayouts, but allscored below ceiling on the Legoobjects. Thus, the true advantage forLego layouts over Lego objects fornormal subjects is probablygreater than that observedhere, in which case GRand CO’s lower performancefor Lego layouts compared to Legoobjects wouldbe even moreabnormal. Furthermore, post -hoc analysesrevealed that oneof the normalsubjects showed adifference in performancebetween Legolayouts and objects that was over2 SDbelowthe mean of the other nine subjects. When this outlying subject was excluded, z-scores were –3.22 for CO and –2.32 for GR.

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 499 EPSTEINET AL.

Figure 10b. Difference between Lego layout performance and Lego object performance for the 1 -back and 5-back conditions. Error bars indicate one 1 SD.

showa memorydeficit for nonsense words,clay objects,or line drawings ofnonsense objects.GR appears tobe slightly impaired on faces and houses, but COperformsnormally on these categories. Strikingly,GR shows aseveredeficit for the real landscapes, performingmore than 40percentage points lowerthan normals.Thus, eventhough thereis someevidence that GRmighthave some impairment fornonscene stimuli, he clearly is much moreimpaired for scene -likestimuli such as the Legoscenes and landscapes. COdoesnot show a similar deficitfor the landscapes. However,it shouldbe kept in mindthat in oneof his twotesting sessions, COviewedeach picturefor 3 s,which was much longerthan the1 secondused for all non - Legostimuli forGR and normals.Thus, CO’s apparently “normal”performance in thesecondi - tions might be overestimated. Taken together,the results ofthis experiment Figure 10a. Results of Experiment 3, for GR (top) CO (middle) indicate that GRand COare selectivelyimpaired at and for 10 age -matched normal controls. Performance measure is processing scene -likestimuli. This deficitis consis - proportion of repeated stimuli correctly identified as such, corrected tentlyapparent at 5 back but not1 back intervals. for guessing using the standard formula. - - This finding suggests that thedeficit should be characterised as amemoryencoding problem. Table 4shows results forall eight stimulus However,the present results donot allow us to classes. Althoughdirect comparisons betweensub - determinewhether the difficulty occurs at memory jectsshould be treated with caution since viewing encodingor at subsequent recognition(see Epstein timefor different items was notthe same foreach &Kanwisher,2001). If GRand COhave ageneral subject, wedonote a fewinteresting patterns. First problemwith recognition of topographicalmateri - ofall, there is littleor no evidence that GRorCO als, thenthey should not be able to recognise scenes

500 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

Table 4. Full results of Experiment 3: Mean proportion correct (corrected for guessing); SDs in parentheses

Lego Land- Lego ClayNonsense Non - scenes scapes Houses objects objects objects Words Faces

1-back GR 1.00 0.94 1.00 1.00 1.00 0.94 1.00 1.00 CO 0.91 0.85 0.91 1.00 1.00 0.79 0.74 1.00 Normals0.96(0.08) 0.95(0.08) 0.93(0.14) 0.96(0.08) 0.96(0.06) 0.99(0.03) 0.98(0.04) 0.97(0.11)

3-back GR –0.03 0.68 0.26 0.47 0.83 0.83 0.75 0.52 CO 0.66 0.81 0.37 0.10 0.94 0.69 0.95 0.81 Normals0.66(0.32) 0.77(0.21) 0.72(0.15) 0.77(0.20) 0.86(0.16) 0.83(0.15) 0.83(0.17) 0.72(0.20)

5-back GR 0.10 0.34 0.44 0.47 0.72 0.83 0.94 0.53 CO 0.31 0.73 0.75 0.88 0.81 0.64 1.00 0.81 Normals0.76(0.26) 0.77(0.16) 0.68(0.21) 0.66(0.16) 0.91(0.14) 0.83(0.18) 0.93(0.11) 0.78(0.21)

and landmarks that werelearned prior to their Method injury. Wetested this possibility in thenext Each ofthetwo experiments (famous faces, famous experiment. landmarks) consistedof 48 trials. Subjects began each trial by pressing thespace bar, after whicha black-and-whitephotograph of a face (in the famous faces experiment)or a landmark (in the famous landmarks experiment)appeared on the Experiment 4: Famous landmarks/faces screen.Subjects weretold to press the“ j”key if they recognition task recognisedthe specific face orlandmark, and the“ f” Inthis experiment,we examined GR and CO’s keyif theydid not, taking as much timeat they ability torecognise the visual appearances ofplaces neededto make this discrimination but noextra learnedprior to injury. Subjects saw aseriesof time.Subjects weretold to reportthat theyrecog - famous landmarks intermixedwith nonfamous niseda face orlandmarkif theyfelt that theyknew controls.(Imaging experimentshave demonstrated it,even if theycould not retrieve its name.If they that landmarks ofthis typecan activate thePPA didknow the name, they were to say itafter pressing almostas stronglyas completescenes; Epstein et thebutton. Otherwise, they were to say whatever al.,1999; Epstein & Kanwisher,1998.) They were they did remember about the item. requiredto say whetherthey knew each specific Halfofthephotographs were of famous and half landmark,and toidentifythe ones they knew. Sub - ofnonfamous peopleand landmarks.The famous jectswere instructed torespondaffirmatively if they faces includedpublic figures (e.g.,George Bush, werefairly certain that theyrecognised the land - Richard Nixon,Prince Charles) and moviestars mark,but notif itonly looked generally familiar. (e.g.,Harrison Ford,Clark Gable,Marlon Brando) For purposes ofcomparison, subjects also per - whowere prominent prior to thetime of GRand formedan identicaltest in whichthe stimuli were CO’s injuries; thefamous landmarks werebuild - famous and nonfamous faces. In bothtests, ings and monuments fromall over the world (e.g., distractor itemswere designed to be visually and EiffelTower, US CapitolBuilding, Great Sphinx). conceptuallysimilar tothe target items(see Figure Thenonfamous stimuli werechosen to match the 11).If parahippocampal cortexis requiredfor place famous stimuli as closelyas possible.Each famous recognition,then one might expect GR and COto stimulus had a“match.”For example,George Bush performpoorly compared to normals onthe land - was matchedto aman ofsimilar age in acoat and mark recognition test. tie,and theTaj Mahal was matchedto a visually

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 501 EPSTEINET AL. S K R A M D N A L Figure 12. Results of Experiment 4. Performance measure is proportion of famous stimuli reported as “known,” corrected for guessing using the standard formula.

GRand COcouldrecognise the famous landmarks as wellnormals. In addition,both GR and COwere usually ableto name thelandmarks theysuccess - fully identified. Thus, GRand COcan recognizelandmarks learnedprior to injury, demonstrating that at least someof theirplace recognition abilities are intact. Whencombined with the fact that GRand CO wereable to produce detailed maps ofplaces they livedin priorto theirinjury (seeCase Description), theseresults suggest that theirdeficit is primarily in

S encodingor consolidation of new information E ratherthan inrecognitionor recallof oldinforma C -

A tion.Note, however, that theseresults donot prove F that theirplace recognition abilities are entirely normal.GR and COmightsuffer froma mildrec - ognitiondeficit that affects identification ofnewly - learnedstimuli likethe Lego layouts inExperiment 3but notoverlearned stimuli likethe famous land - marks. Furthermore,it is possiblethat GRand CO mightbe impaired at recognising premorbidly Figure 11. Stimuli for Experiment 4. Each famous landmark learnedplaces that are definedprimarily by their (Arc de Triomphe, Taj Mahal) and famous face (Barbara Bush, spatial layouteven though they are unimpaired at Yasser Arafat) was matched to a nonfamous building or face that recognising premorbidlylearned places that are also appeared in the experiment. definedprimarily by asingleobject -likelandmark orbuilding (seeGeneral Discussion). Nevertheless, similar Asian palace that isnotfamous (seeFigure thetrend of the present evidence is tosuggest that 11). GRand COhave particular problemswith novel topographical information. Results and discussion Inthe famous -face task, GR’s performancewas Results forGR and CO, as wellas forfive age - in thenormal range. However, he sometimes had matchedcontrols, are shownin Figure 12.Both difficulty naming thefaces eventhough he clearly

502 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING recognisedthem. For example,he described Ron - Epstein& Kanwisher,1998) convergeto implicate aldReagan as “thegipper,” Nancy Reagan as “the parahippocampal cortexin theencoding of infor - wifeof thegipper,” and Clark Gable as “themovie mation about scene geometry into memory. actor whosaid, ‘Scarlett,I don’t givea damn’” .CO Our assignment ofthe function ofmemory had agreat dealof difficulty identifying thefamous encodingto parahippocampal cortexis consistent faces. This resultis notsurprising given his withthe results ofearlier case reportsof patients extremelylow performance on the Benton Face withparahippocampal damage whohave naviga - Matching Task. In additionto his topographic tionaldifficulties in novelbut notfamiliar environ - problems,CO appears tosuffer from ments (Habib &Sirigu,1987; Ross, 1980;see also prosopagnosia. Teng &Squire,1999). As withGR and CO, these patients wereeither less impaired or unimpaired on nontopographicalmemory tasks. Patients have also GENERAL DISCUSSION beendescribed who exhibit the opposite pattern of impairment:an inability tolearn faces (sometimes Wetested two parahippocampal patients (GR and called“ prosopamnesia,”Cipolotti, Robinson, Blair, CO) onfour experimentsdesigned to measure per - &Frith, 1999;Tippett, Miller, & Farah, 2000),or formance as afunction ofboth task (perception, faces and verbal materials (Maguire &Cipolotti, encoding,and recognition)and stimulus type 1998),with an unimpaired ability tolearn topo - (scenes, objects,faces, and words).The only task graphical materials. Taken together,these results that revealeda cleardeficit was an n -back recogni - argue fora high degreeof domain -specificity in the tionmemory test (Experiment 3). In orderto suc - neural systems involvedin learning ofnew informa - cessfully performthis task, subjects had toencode a tion(Gallistel, 1995). The brain may have separate durablerepresentation of a visual stimulus and use mechanisms forlearning faces, places,and words, itfor later recognition. GR and COweresignifi - whichcan bedifferentially impaired after damage cantly moreimpaired on this task whenthe stimuli tospecific corticalregions (Cipolotti et al., 1999; were scene-likespatial layouts (i.e.,Lego scenes, Incisa dellaRochetta et al., 1996). The present and realscenes forGR) than whenthey were results suggest that theanatomical locusof the objects.No comparable deficits werefound in other mechanism dedicatedto learning newtopographi - experimentsthat testedlayout perception (Experi - cal information is in theparahippocampal cortex ments 1and 2)and place/landmarkrecognition (Aguirre & D’Esposito, 1999). (Experiment4). Taken together,these results indi - In contrast totheir impaired ability toencode cate that GRand COare impairedin theirability to newtopographical information, both GR and CO encodenovel information about thegeometry of wereable to produce detailed maps oftheirprevious surrounding space intomemory, but are less dwellings,and performednormally on thefamous impairedat theirability toencode the geometry of landmarkrecognition test of Experiment4. These novel objects. results are generallyconsistent withTeng and Weargue that this specific topographicaldefi - Squire’s (1999)report of a patient withextensive cit—inability toencode the spatial layoutof novel medialtemporal damage whocould recall scenes—results fromdamage tothe para - premorbidlylearned but notpostmorbidly learned hippocampalplace area. Althoughthe damage in topographicalinformation (seealso Ross, 1980). bothpatients extendsbeyond the parahippo - Thus, ourresults providefurther evidence that campal-lingual territorynormally associated with medialtemporal regions such as parahippocampal thePPA, this regionis clearlylesioned bilaterally in cortexmay bemore critical forencoding or consoli - GRand in theright hemispherein CO. Further - dating newinformation intomemory than forrecall more,functional imaging demonstratedthat GR of old information. has nofunctioning PPA.Thus, thecurrent results One issue that ourexperiments do notentirely and theearlier fMRI work(Epstein etal., 1999; resolveis theprecise nature ofthe topographical

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 503 EPSTEINET AL. information encodedby parahippocampal cortex. parahippocampal cortex,but by moreposterior lin - Clearly,this regionis critical forencoding informa - gual-fusiform regions.In contrast, webelievethat tionabout thegeometry of the currently visible theneuroimaging data indicate that parahippo - sceneeven when the “ scene”is madeout of Lego campal cortexis involvedin theencoding of the blocksand thereforehas noimmediate navigational geometricstructure ofindividual scenes,although relevance.However, it is unclear whetherthis spe - itmay also play arolein combining theserepresen - cific deficitcan account forall of the real -world tations with other spatial representations. navigational difficulties encounteredby GRand Interestingly,GR and COwerenot impaired on CO. GRin particular shows such acatastrophic recognitionof famous landmarks that weremostly lossof navigational ability that wesuspect heis also buildings. Thus, ourdata donotpreclude the possi - impairedat encodingthe spatial relationships bility that theremay bea separate lingual or betweenthe current sceneand otherlocations in the fusiform regioninvolved in processing information world.CO probably also suffers fromsuch difficul - about buildings (Aguirre,Zarahn, &D’Esposito, ties,as hereportsthat hehas troubleremembering 1998;Chao, Haxby, &Martin, 1999;Ishai, howplaces relateto each otherin large -scale space. Ungerleider,Martin, Schouten,& Haxby, 1999) Whenhe was testedon a simple3 -roomvideogame whichmight have beenpreserved in GRand CO environment,he notonly was unable toremember despiteextensive damage toother regions of the theindividual rooms(claiming that therewere 10 lingual and fusiform gyrus. Alternatively,GR and roomswhen there were only 3), but healso had no CO’s preservedbuilding recognitionabilities might memoryfor the spatial relationships betweenthem. bemediated by interactions betweencortical areas Thesespatial deficits may bethe result of damage to that performshape analysis forany object -like theposterior right hippocampus (in thecase ofCO) stimulus type(Malach etal.,1995; Kanwisher etal., orof disconnection of the posterior right hippo - 1996)and anteriortemporal regions in whichlong - campus fromthe parahippocampal regionsthat termtopographical and semantic memoriesare providemuch ofits corticalinput (in bothpatients; stored (McCarthy et al., 1996). Suzuki &Amaral,1994). In eithercase, theability toform a cognitivemap ofnewenvironments like Is perception preserved? thelab orvideogame space couldbe impaired (Maguire etal., 1998; O’ Keefe& Nadel,1978). In contrast totheir inability toencode new scenes However,it is alsopossible that parahippocampal intomemory, GR and COhave substantially cortexitself may becritical forencoding not only retainedtheir ability toperceivethe spatial layoutof thegeometry of individual scenes but also thespa - thecurrently visible scene(Experiments 1 and 2). tialrelationships betweenthe locations of those GRcan followa routemarked on a floorplan, scenes.In this case, thespatial deficits ofGRand whichindicates agoodon -lineappreciation ofhis COcouldbe attributed directlyto parahippo - current spatial surroundings. Furthermore,neither campal damage ratherthan tohippocampal dam - GRorCO have any troublemoving throughthe age or disconnection. environment—they move with confidence and do Thelatter scenario wouldbe consistent with notbump intodoors or walls.Problems of thelatter Aguirreand D’Esposito’s (1999)and Barrash et typeare usually associated withdamage tothe pari - al.’s (2000)suggestion that parahippocampal cortex etallobes, which are intact in GRand CO. Thus, at is critically involvedin combining visual informa - first glance,GR and COdonot appear tohave tionabout theappearance ofscenes and landmarks perceptualimpairments (beyondtheir visual field withspatial information about theirlocations into a restrictions). unified topographicalrepresentation. However, However,GR doescomplain of a perceptual bothof these authors argue that therepresentations deficit,which he describes as an inability to“ take ofindividual scenes (Barrash etal.) and landmarks in”scenes whenthey are toocomplex. Similar (Aguirre &D’Esposito) are supportednot by reportsof an inability tocomprehend the

504 COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) PARAHIPPOCAMPUS &TOPOGRAPHICALLEARNING

“globality”of a scenewere made by someof the tionof episodic memories (cf., Wagner etal., parahippocampally -damagedpatients studiedby 1998). Habib and Sirigu (1987).We were not able to In previous work(Epstein etal., 1999), we determinethe precise nature ofthis deficit,which argued that spatial contextinformation encodedby may bepartly attributable tohis visual fieldrestric - parahippocampal cortexmight play arolein estab - tions.It appears that his deficitis moresalient in the lishing eventmemories by encodinginformation real-worldenvironments than in thepicture -per- about whereevents take place. The inability to ceptiontasks ofExperiments 1 and 2,perhaps encodethis information mightcause problemsin because hefinds it moredifficult toorganise visual tasks such as theRey AVLT,where one has torecall input whenimmersed in itthan whenviewing pho - alistof unrelated words: If spatial (and perhaps tographs that subtend onlypart ofthevisual field. temporal)context information is notencoded, it Wesuggest that GRcan perceiveparts ofthe willbe harder subsequently torecall the distinct scenewhen he attends tothem, but may beunable eventof hearing each word(Tulving, 1983).In tointegrate information overtime into a coherent contrast, lackof spatial contextinformation would representationof a sceneor place.The fact that GR beless of a problemin tasks whereone is only and COare impairedfor Lego layouts at 5 -back requiredto recognise previously encountered verbal intervals in Experiment3 is consistent withthis materials but notto reproducethe spatiotemporal hypothesis.The time between the first and second contextin whichthey were experienced. Indeed, presentations ofastimulus is veryshort in this case GRand COperformedas wellas normals onthe (and evenshorter with 3 -back intervals, whereGR nonsense wordsin Experiment4, where recogni - also shows evidenceof adeficit).In bothpatients, tionmemory but notepisodic memory was required therepresentation of layout information formedby forsuccessful performance.Interestingly, GR and perceptionof a Legoscene must eitherhave an COalso didrelatively well on theLogical Memory abnormally shortpersistence, be abnormally sus - subtest oftheWMS -III,perhaps because thenar - ceptibleto interference, or both.If so,they might rative frameworkof astory providessufficient con - find itimpossible to sustain aspatial frame or textualinformation toovercome the absence of schema longenough to use it toorganise informa - spatial contextand mediatesuccessful verbal tionobtained from many differentglances at acom - retrieval. plexscene (Intraub, 1997).The result would be an inability tounderstand the“ globality”of a scene, Differences between GR and CO eventhough all the details were perfectly perceived. Althoughwe have discussed GRand COtogether, thereare anumber ofrelevantdifferences between Non-topographical mnemonic abilities them.One openquestion iswhetherthese differ - Althoughnot as severeas theirtopographical mem - encescan beattributed tothe different effects of oryproblems, GR and COdohave somememory unilateral and bilateralparahippocampal damage. difficulties in otherdomains. For example,both Ingeneral, GR’ s topographicaldifficulties were performedpoorly on the Rey AVLT,which moresevere than CO’s. COdidsurprisingly wellon requiredthem to remember a listof unrelated theWarrington Topographical MemoryTest, in words.Both also reportsome subtle episodic mem - whichhe was requiredto remember detailed real - oryproblems (see Case Description).CO’ sprob - worldcity scenes,and alsoperformed substantially lemscould partly resultfrom damage totheright betteron real scenes than Legoscenes in Experi - hippocampus—indeed, CO appearedto have the ment3. Insofar as COhas intact leftpara - moreacute episodicmemory problems. However, hippocampalcortex, this suggests that theleft PPA GRhas nohippocampal damage, so the fact that he mightbe sufficient toencodea certain amount of displays episodicmemory problems suggests that (perhaps semantic) information about real -world parahippocampal cortexis involvedin theforma - scenes,but theright PPAis necessary toencode

COGNITIVE NEUROPSYCHOLOGY,2001,18 (6) 505 EPSTEINET AL.

Legoscenes that must berecognised solely on the ing”stimuli: Evidence and implications. Neuron, 21, basis oftheirspatial structure. Clearly,however, the 373–383. amount oftopographical information that can be Barrash, J.,Damasio,H., Adolphs, R., & Tranel, D. encodedusing onlya leftPPA is strictly limited. (2000).The neuroanatomical correlates ofroute Anotherdifference between the two patients is that learning impairment. Neuropsychologia, 38 , 820–836. Beauchamp, M.S.,Haxby, J.V.,Rosen, A.C., & DeYoe, GRreportssome kind of perceptualproblem, but E.A.(2000). Functional MRIcorrelates ofrecovery COdoesnot. It is presentlyunclear whetherthese offunction in acquired cerebral dyschromatopsia. differencesare indicative ofqualitatively different Neuropsychologia, 38, 1170–1179. kindsof impairment after unilateral and bilateral Bohbot,V., Kalina,M., Stepaknova,K., Spackova,N., lesions,or whetherthe same abilities are affectedin Petrides,M., &Nadel,L. (1998).Spatial memory bothcases but toa moresevere degree with bilateral deficitsin patients with lesionsto the right hippocam - lesions. pus and tothe right parahippocampal cortex. Neuropsychologia, 36 , 1217–1238. Chao,L.L., Haxby, J.V.,& Martin, A.(1999).Attrib - Conclusion ute-based neural substrates in temporal cortexfor perceiving and knowingabout objects. Nature Neuro - Weexamined two patients withlesions to science, 2, 913–919. parahippocampal cortex.Both exhibited severe Chen, L.L.,Lin,L.H., Green, E.J.,Barnes, C.A.,& topographicaldifficulties, particularly in newenvi - McNaughton,B.L. (1994).Head direction cellsin ronments.A keycomponent of theirproblem is a the rat posterior cortex,I. Anatomicaldistribution memoryencoding deficit that is moresevere for and behavioral modulation. Experimental Brain visual stimuli that depictspaces that onecan navi - Research,101 , 24–34. gate throughor act within than forother visual Cheng, K.(1986).A purely geometric modulein the rat’s materials.We found no clear evidence that spatial representation. Cognition, 23 , 149–178. Cipolotti,L., Robinson,G., Blair,J., &Frith, U.(1999). parahippocampal cortexis necessary forthe initial Fractionation ofvisual memory: Evidence fromacase perceptualprocessing ofvisual scenes,recognition with multiple neurodevelopmental impairments. oflandmarks, orrecallof premorbidly learned top - Neuropsychologia, 37, 455–465. ographical information.Parahippocampal cortex Eichenbaum, H.,Dudchenko,P., Wood,E., Shapiro, may bethe neuroanatomical locusof a learning M.,&Tanila, H.(1999).The hippocampus,mem - mechanism preferentiallyinvolved in theencoding ory,and placecells: Is it spatial memory oramemory of topographical materials into memory. space? Neuron, 23, 209–226. Epstein, R.,Harris, A.,Stanley,D., &Kanwisher, N. Manuscript received 20 December 1999 (1999).The parahippocampal placearea: Recogni - Revised manuscript received 14 June 2000 tion, navigation, or encoding? Neuron, 23, 115–125. Revised manuscript accepted 20 October 2000 Epstein, R.,&Kanwisher, N.(1998).A corticalrepre - sentation ofthe localvisual environment. Nature, 392, 598–601. Epstein, R.,&Kanwisher, N.(2001). Mnemonic func - REFERENCES tions ofparahippocampal cortex:An event -relatedfMRI study. Manuscript submitted for publication. Aguirre G.K.,& D’Esposito,M. (1999).Topographical Evans, A.C.,Collins, D.L., Mills, S.R., Brown, E.D., disorientation: Asynthesis and taxonomy. Brain, 122, Kelly,R.L., & Peters, T.M.(1993).3D statistical 1613–1628. neuroanatomical modelsfrom 305 MRI volumes.In Aguirre, G.K.,Detre, J.A.,Alsop, D.C., & D’Esposito, Proceedings of the IEEE -Nuclear Science Symposium M.(1996).The parahippocampus subserves topo - andMedical Imaging Conference (pp. 1813–1817). graphical learning in man. Cerebral Cortex, 6 , 823– Gallistel,C.R. (1990). The organization of learning . 829. Cambridge, MA: MIT Press. Aguirre, G.K.,Zarahn, E.,&D’Esposito,M. (1998).An Gallistel,C.R. (1995). The replacement ofgeneral -pur- area within human ventral cortexsensitive to“ build - posetheories with adaptive specializations.In M.S.

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