98ournal ofNeurology, Neurosurgery, and Psychiatry 1993;56:988-992

Retrograde amnesia after traumatic injury of thefronto-temporal cortex

H J Markowitsch, P Calabrese, J Liess, M Haupts, H F Durwen, W Gehlen

AbstractAn industrial manager had severe retro-grade and variable but usually mildanterograde amnesia four years after ahead injury. MRI showed damage ofbothtemporal poles and the lateral portion ofthe right prefrontal cortex. The pre-frontal and temporal cortical damage onthe right side extended deeply into thewhite matter while the temporal corticaldamage on the left side was muchsmaller. There was an additional lefttemporo-parietal lesion. The patient wasof average intelligence. His attention,short term memory and learning abilitywere average or somewhat below aver-age. His old memories were severelyaffected for the personal-episodicdomain and less so for semantic remotememory abilities. Therefore an anatomi-cal dissociation between anterograde andretrograde amnesia is possible at theanterior temporal regions, possiblyinteracting with the prefrontal cortex;these regions seem necessary for theretrieval of old episodic memories.

(3 Neurol Neurosurg Psychiatry 1993:56:988-992)

PhysiologicalPsychology,University ofBielefeld, GermanyH J MarkowitschP CalabreseJ LiessNeurologicalUniversity Hospital,Bochum-Langendreer,GermanyP CalabreseM HauptsH F DurwenW GehlenCorrespondence to:HJ Markowitsch,Physiological Psychology,University of Bielefeld,PO Box 100131, D-33501Bielefeld

Received 13 July 1992and in revised form19 October 1992.Accepted 20 November 1992

There are now descriptions of several cases ofdissociation of anterograde and retrogradeamnesia.'-" In most of these cases the dam-age to the brain was the result of traumaticinjury and can therefore be seen as resem-

bling that described in several earlier reportsin which concussions of the brain were fol-lowed by severe old memory disturbances.'2-2'Last century a number of reports alreadydealt with the phenomenon of retrograde

22-24amnesia. -

Characteristic for most of the recent caseswith dominant retrograde amnesia is the vari-ability of their brain damage and the relativelybetter preserved semantic or priming-relatedremote memory compared with the severelyaffected episodic old memories. (Semanticmemory refers to general knowledge about theworld, for example, grammar, mathematicalrelations, chemical formulas; priming to "sub-conscious" knowledge or facilitated identifi-cation of information previously exposed to,and episodic memory to personal, temporallydated events.) In some case descriptions theretrograde amnesia related brain damage wasidentified in the junction zone of pons andmesencephalon,2' in the temporal, includingthe entorhinal cortex,6 in the temporo-parietal

cortex,'011 25 in the temporo-polar cortex,7 8and Kopelman26 27 favoured the prefrontalcortex as the principal target region impli-cated in the retrieval of remote memories. Inhis 1991 article, Kopelman27 specifically sug-gested that "dorsolateral frontal lesions(occurring in combination with limbic-dien-cephalic pathology) may account for an im-poverished retrieval of retrograde memories."

Case reportA 45 year old male patient had had a severetraumatic brain injury four years earlier,caused by falling off a horse. He had beencomatose for about six weeks. Before his acci-dent the patient had been employed as amanager in a big company. He had beenreferred to us because of his persistent retro-grade memory deficits. His present neuro-logical status was examined with MRI and hisneuropsychological status was tested duringseveral sessions, over three days.Most of the behavioural findings of the

patient are compared with those of a normalsubject of an age of 52 years, comparableintelligence, and a similar occupational posi-tion as the patient. For the retrograde mem-ory tests additional comparisons were used.For the Autobiographical Memory Interview28reference is made to the cut-off scores pro-vided in that test. Results in the FamousFaces Test29 are compared with those of asample of control subjects tested by U Schuri(City Hospital Munich-Bogenhausen), andfor the Famous names test we collected ourown data by testing five normal subjects ofcomparable or lower educational backgroundand age.

NEURORADIOLOGICAL EXAMINATIONMRI of his brain was performed using serialTi and T2-weighted coronal and axialimages (6 and 7 mm slices). Both temporalpoles, with preference to the right hemi-sphere, were severely affected. Furthermore,the basal and lateral part of the right temporallobe was damaged, sparing, however, themedial temporal lobe structures, includingthe hippocampal formation, on both sides(fig). Major brain damage was found in thefronto-basal cortex with preference to theright side. Additionally, an extensive cortico-subcortical lesion was situated in the left tem-poro-parietal transition zone.

NEUROPSYCHOLOGICAL EXAMINATIONThe neuropsychological tests and a summary

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Retrograde amnesia after traumatic injury of the fronto-temporal cortex

Figure The principalbrain damage in coronaland axial views. a-d:Coronal T2-weighted MRIscans showing the mainportions of the damage inthe prefrontal and temporallobes from anterior toposterior. 'R' and 'L'denote the left and righthalves of the brain. e:Magnification of themedial temporal area of thesection shown in d todemonstrate preservation ofthe hippocampalformation. f, g: HorizontalT,-weightedMRI scansshowing the main portionsof the damage in theanterior and lateraltemporal lobes.

of the results are listed in table 1. Theyincluded tests of intelligence, attention, con-centration, sensory and language functions,and various forms of memory tests. A numberof these tests had been used and described indetail in a previous publication of a case withbilateral thalamic damage.30The patient appeared to be alert, and inter-

ested. He made suggestions, was socially

well-adjusted, and was able to interact in vari-ous ways with his environment. Wheninstructed, he could remember to do some-thing or to go to a certain place. In formaltesting, he gained an IQ of 100 points, hisattention, measured by three tests, wasslightly below average. In the Wechsler-Memory-Scale-R he received 85 points forthe General-Memory-Index. The other values

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Table 1 Neuropsychological tests used

ControlPatient subject(s)*

INTELLIGENCE 100ATTENTION (3 tests) averageMEMORY IN GENERALWechsler-Memory-Scale-R (General-Memory-Index) 85Rivermead Behavioural Memory Test (German form) 76/150SHORT TERM MEMORY (Corsi-block-tapping; Digit span) 5; 4CONCEPT FORMATION, COGNITIVE FLEXIBIITY,ABILITY TO CALCULATE

WCST (categories achieved; perseverative errors) 2; >18Tower ofHanoi (4 disc version) (trials needed; perseverative errors) 39; 4Concept formation task 18/20Fibonacci series averageSimple calculations averageTest requiring to transcode numbers averagePRIMING TASKSGollin Incomplete Figures Test (3 sessions)average level of identification:

(1st presentation) 7-3(2nd presentation) 6-2(3rd presentation) 4 9

Word stem completion (2 lists) 60%Mirror image reading (1st, 2nd presentation in s) 5-7, 3-2RETROGRADE MEMORYFamous Faces Test (see text for a comparison with control subjects' performance):

1946-55 (from 20 faces correctly recognised) 13/201956-65 10/201966-75 9/201976-85 6/201986-92 13/20

Famous names 33/60Semantic Knowledge Test 70/100Autobiographical Memory Interview:

personal semantic events 31-5/63autobiographical incidents 6/27

Personal Objects Test (individual episodic remembrance of owned objects)1956-65 4/51966-75 3/51976-85 1/5

LONG TERM MEMORYVerbal Recognition Test (similar to RBMT) 5/10Rey-Osterrieth-Figure (complete value: 36)

copy; immediate reproduction; delayed reproduction 24; 14; 7Verbal Learning ofNew Facts

(contents of 13 sentences after 2 days delay) 7/13

*For the Famous Names Test the patient's results were compared with those of anormal, age-matched control subjects (mean age = 51 years) of comparable ortional level. Their mean value was 57-8 points.

were 85 (Verbal-Memory-Index), 9Memory-Index), 72 (Attentiortration) and 67 (Delayed RecallGerman version of the IBehavioural Memory Test (RBM'below average, gaining 76 of 154points. His short term memory was

In tests measuring cognitive flexconcept formation ability, thebehaviour varied greatly. In theCard Sorting Test he was poor, inmof Hanoi Test below average, and iformation and mathematical abilitiaverage (see table 1). Both verbalverbal priming tasks gave evidenceally normal learning abilities underconditions.

RETROGRADE MEMORYAs the main complaint of the patiwas that her husband "is unable tonearly anything from his life beforndent", we put particular emphasishis retrograde memory abilities. 'that he had major memory diewhich were most noticeable formemory, but also extended to hknowledge. (table 2).

For testing general knowledge, i

German version of the WarringtoiFaces Test29 (provided by U Schurtest the patient is given portraits of

110average

110112/1505; 4

7; 015; 019/20averageaverageaverage

6-64-3

Table 2 Performance (points) of the patient and thecontrol subject in the Autobiographical Memory Test

Control Cut-offPersonal semantic events Patient subject scores [31]*

Childhood 6 18 <11Early adulthood 12 19-5 <14Actual life 13-5 21 <17Sum (max.: 63 points) 31-5 58-5 <47Autobiographical incidentsChildhood 0 9 <3Early adulthood 0 9 <3Actual life 6 9 <5Sum (max.: 27 points) 6 27 <12

*The cut-off scores refer to "definitely abnormal" values; thismeans that the only not definitely abnormal (but "border-line") value was seen for the patient's recent autobiographicalincidents, that is, for the current (post-injury) time period.

2-9 of people (actors, politicians, sportsmen, etc)65% from different time periods, and he or she has

to produce the name of the respective subject.19/20 In scoring his (and the control subject's) per-19/20 formance, we also gave points when a correct19/20 answer was given after helping the subject by15/20 presenting initials or first names. The patient98/100 was rated poor for the intermediate time peri-58-5/63 ods, but showed a gradient for remembering27/27 of famous faces from different decades (table

1). Compared with a sample of control sub-5/5 jects that were tested, the only values in a5/5 normal range were found for the first and the10/10 last time period tested. We attributed the

normal remembrance for the last time period21; 20; 10 to his less affected anterograde memory abili-10/13 ties, as his injury occurred in 1987.sample of five A similar performance was found for thelower educa- Famous Names Test in which blocks of sev-

eral names were given and the subject had toidentify that of a person who was famous dur-ing a given epoch (multiple choice).

1 (Visual- In a third measure, the Semantic Generaln-Concen- Knowledge Test (names of countries, curren-). In the cies, cities, famous subjects, etc), the patientRivermead gained 70 out of 100 possible points whichI) he was reflected an existing semantic or even priming0 possible memory, similar to the patient described byaverage. Damasio et al.31ibility and Fourthly, the German language adaptationpatient's of the Autobiographical Memory Interview28

Wisconsin was given. The patient was clearly impairedthe Tower in this test, but knew several overlearned per-in concept sonal and a few autobiographical facts. Theies he was only score that was better than "definitelyand non- abnormal" (according to the score byfor gener- Kopelman et al 28) was shown for his recentthe tested past, that is, the post-injury time period.

For the last test we collected from thepatient's wife a number of personal objectswhich the patient had used during different

ient's wife time stages before and after his accidentremember (Personal Objects Test). Of these we tooke his acci- five appropriate objects. For each of these fiveon testing objects, verifiable and unequivocally dissocia-We found tive events were expected. Scoring was car-sturbances ried out as follows: The first point was givenpersonal when the object was correctly recognised as a

Lis general personal belonging. Each further detail wasgiven a point. For example, the patient had

we used a bought a pocket watch (1st point) forn Famous Christmas 1982 (2nd point) for a horrendousri). In this price (3rd point) at an exceptional hour of thea number day (4th point), and had later given it to his

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Retrograde amnesia after traumatic injury of the fronto-temporal cortex

wife as a Christmas gift (5th point). Thoughthere were some favoured objects among thiscollection, the patient recognised only thosefrom the earliest (1956-65) and half of thesecond time period (1966-75) as belongingto him; for the last term before his brain dam-age (1975-86) he recognised only one object.For reported details, he gave four altogether,three, and one for the three time periods. Inthe period between his injury and the presenthe again recognised four objects; all the fourhe recognised were from the period after hisbrain damage, while the fifth, unrecognised,was from the epoch before his accident.As an example of a possible dissociation

between semantic and episodic memory, ourpatient when questioned about the location ofMount Kilimanjaro answered that it was situ-ated in Tanzania. He did not remember thathe had climbed its peak shortly before hisaccident. (This fact is particularly interestingas most people would be unable to name thecountry, and of the few who could, mostwould probably think of Kenya instead. Infact, it is situated in both countries, but thepeak can only be reached from the Tanzanianside.) Another example is that he had beenable to understand and to speak Italian on anadvanced level before the trauma, but deniedhaving any significant knowledge of theItalian language. As the principal examiner(PC) is a native Italian speaker, it was possi-ble to test this statement by requesting thepatient to follow some instructions given inItalian. The patient executed all verbalinstructions correctly so that at least heunderstood this foreign language and couldtherefore respond to it at the level of priming.

Also his procedural memory remainedlargely intact giving a further example for dis-sociations among memory systems. Thepatient had been an avid car-driver since hisyouth and was able to drive before he was oldenough to apply for a licence. After his acci-dent he took some driving lessons and wasstill considered capable of managing a car.

DiscussionOur patient can be considered a typicalexample of a case with dominant, but notexclusive, retrograde amnesia. Furthermore,his retrograde memory disturbances are un-equal with respect to true autobiographicaland more impersonal, or semantic memoryrelated knowledge. The formal test results onretrograde memory provide some support forthis distinction (for example, considerableknowledge in the Semantic Knowledge Test,much better performance in the Auto-biographical incidents as opposed to thePersonal semantic events part of theAutobiographical Memory Interview), thoughnot all results were clear-cut in this direction(for example, Famous Faces Test). Clear evi-dence for this dissociation comes from theeveryday life examples (such as, knowledge ofthe geographical locus of Mount Kilimanjaro,no remembrance of having climbed it him-self). The patient's mnestic functions were

remarkably similar to those of Tulving'spatient.'2Our patient showed the possible relations

between retrograde memory disturbances andcertain brain foci. It is very unlikely that anymedial temporal lobe damage existed whichcould have contributed to his deficits. Hisdamage nevertheless was not restricted to onefocus, but included a combination of bilateraltemporal and right-sided frontal damage.Very similar to the case given by Kapur et a18the temporal damage had its focus in thepolar region and included some further,partly frontal, damage.We conclude from the overall picture of his

anatomical damage and from comparing hiscase with those described previously that thetypical case with dominant retrograde amne-sia can be characterised by a dominant (bilat-eral) temporo-polar focus with someadjacent, usually frontal-lobe, damage. Thisimplies that the pathways interconnecting theanterior temporal cortex with the rest of the(association) cortex are severely disrupted.This may hold particularly to the uncinatefascicule, but also to pathways interconnect-ing the cingulate, retrosplenial, posterior tem-poral, and parietal cortex with the anteriortemporal cortex. We cannot decide, to whatdegree the interruption of fibres relating theanterior temporal cortex to regions of amyg-dala and hippocampus and to thalamic nucleiare of importance. However, the findings byIwai and Mishkin33 that the more anterior thetemporal cortex is lesioned the more it affectsmemory, seems to receive new relevance, asdo the recent findings by Sakai andMiyashita34 who suggested from their electro-physiological recordings in the anterior tem-poral cortex of monkeys that this regionmight be "activated in the retrieval process"of memorised events.We also cannot specify the role of the

frontal cortex in the context of retrogradeamnesia. The role of this structure in time-sequencing behaviour and in the ordering ofinformation and therefore in relating it tocontext and to order information along thedimension time, seem mechanisms which willvery likely contribute to a proper memorisingof remote information.3-7

In most of the cases described as havingdominant retrograde amnesia, the aetiologyof the brain damage is a traumatic one,involving a severe, sudden concussion whichaffects the brain along its anterior-posterioraxis.'4 1619 Cases of amnesia pugilistica andamnesia after playing football may be simi-larly affected.'2 13 15 20 21 38

Descriptions of patients with totally intactanterograde amnesia, but severe retrogradeamnesia are very rare and to date are not welldocumented. It therefore may be assumedthat there is an interaction between bothforms of amnesia, with the condition of moresevere anterograde than retrograde memorydefects being the most frequent, but not anecessary one. Especially under conditions ofconcussion- and coma-accompanied trau-matic brain injury with an involvement of the

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temporal cortex (including its antero-lateralportion), the reverse deficit pattern, namely asevere retrograde and a mild anterogradememory impairment, may occur. It seems tobe characteristic for these cases that the con-dition is stable so that there is little hope of(insight-related) improvement of remotememories.We conclude from our present results and

from those of previous studies that a severeinterruption of the cortical fibre networkinterconnecting the anterior and posteriorassociation areas of the cerebral cortex is alikely basis for remote memory impairments.A principal dissociation of anterograde andretrograde memory processing may thereforebe possible on the neuroanatomical level. Themedial portions of the temporal lobe includ-ing and surrounding the hippocampus maybe necessary (though not sufficient) for thecorrect processing of new information, whilethe more lateral and anterior, largely neocor-tical portions may be necessary for theretrieval of memories.We thank the patient and his wife for their cooperation andProfessor L Heuser, Director of Radiology, Knapp-schaftskrankenhaus Bochum-Langendreer, for performingMRI. David Emmans deserves thanks for improving theEnglish of the manuscript. The work reported here was sup-ported by a grant of the German Research Council (DFG; Ma795/9-3).

1 Andrews E, Poser CM, Kessler M. Retrograde amnesiafor forty years. Cortex 1982;18:441-58.

2 Goldberg E, Antin SP, Bilder RM Jr, Gerstman LJ,Hughes JEO, Mattis SC. Retrograde amnesia: possiblerole of mesencephalic reticular activation on long-termmemory. Science 1981;213:1392-4.

3 Goldberg E, Hughes JEO, Mattis S, Antin SP. Isolatedretrograde amnesia: Different etiologies, same mecha-nisms? Cortex 1982;18:459-62.

4 Roman-Campos G, Poser CM, Wood FB. Persistent ret-rograde memory deficit after transient global amnesia.Cortex 1980;16:509-18.

5 Stuss DT, Guzman DA. Severe remote memory loss withminimal anterograde amnesia: A clinical note. BrainCognit 1988;8:21-30.

6 O'Connor M, Butters N, Miliotis P, Eslinger P, CermakLS. The dissociation of anterograde and retrogradeamnesia in a patient with herpes encephalitis. J ClinExptal Neuropsychol 1992;14:159-178.

7 Kapur N, Young A, Bateman D, Kennedy P. Focal retro-grade amnesia: a long term clinical and neuropsycholog-ical follow-up. Cortex 1989;25:387-402.

8 Kapur N, Ellison D, Smith MP, McLellan Burrows EH.Focal retrograde amnesia following bilateral temporallobe pathology. Brain 1992;115:3-85.

9 Sloman SA, Hayman CAG, Ohta N, Law J, Tulving E.Forgetting in primed fragment completion. J ExptalPsychol: Learn Mem Cognit 1988;14:223-39.

10 Tulving E, Schacter DL, McLachlan DR, Moscovitch M.Priming of semantic autobiographical knowledge: A

case study of retrograde amnesia. Brain Cognit 1988;8:3-20.

11 Tulving E, Hayman CAG, MacDonald CA. Long-lastingperceptual priming and semantic learning in amnesia: acase experiment. J Exptal Psychol: Learn Mem Cognit1991;17:595-617.

12 Blonstein JL, Clarke E. Further observations on the med-ical aspects of amateur boxing. Lancet 1957;i:362-4.

13 Critchley M. Medical aspects of boxing, particularly froma neurologlcal standpoint. BMJ 1957;1:357-66.

14 Fisher CM. Concussion amnesia. Neurology 1966;16:826-30.

15 Grahmann H, Ule G. Beitrag zur Kenntnis der chronis-chen cerebralen Krankheitsbilder bei Boxern. PsychiatrNeurol 1957;134:261-83.

16 Russell WR. Amnesia following head injuries. Lancet1935;ii:762-3.

17 Russell WR The traumatic amnesias. Oxford: OxfordUniversity Press, 1971.

18 Russell WR, Nathan PW. Traumatic amnesia. Brain1946;69:280-300.

19 Symonds, C. Concussion and sequelae. Lancet1962;i: 1-5.

20 Yarnell PR, Lynch S. Retrograde memory immediatelyafter concussion. Lancet 1970;i:863-4.

21 Yarnell PR, Lynch S. The "ding": Amnestic states in foot-ball trauma. Neurology 1973;23:196-7.

22 Burnham WH. Retroactive amnesia: illustrative cases anda tentative explanation. AmJPsychol 1903;14:382-96.

23 Dana CL. The study of a case of amnesia or "double con-sciousness". Psychol Rev 1894;1:570-80.

24 Markowitsch HJ. Intellectual functions of the brain. An his-toricalperspective. Toronto: Hogrefe and Huber, 1992.

25 De Renzi E. Focal retrograde amnesia: a PET study.Conference: "Anatomy of amnesia", Manchester 10-12,1992.

26 Kopeiman MD. Remote and autobiographical memory,temporal context memory and frontal atrophy inKorsakoff and Alzheimer patients. Neuropsychologia1989;27:437-60.

27 Kopeiman MD. Frontal dysfunction and memory deficitsin the alcoholic Korsakoff syndrome and Alzheimer-typedementia. Brain 1991;114:117-137.

28 Kopelman MD, Wilson BA, Baddeley AD. The autobio-graphical memory interview: A new assessment of auto-biographical and personal semantic memory in amnesicpatients. J Clin Exptal Neuropsychol 1989;11:724-44.

29 Warringtron EK. Recognition memory test. Windsor, UK:NFER-Nelson, 1984.

30 Markowitsch HJ, von Cramon DY, Schuri U. The mnes-tic performance profile of a bilateral diencephalic dam-aged case with preserved intelligence and severeamnesic disturbances. J Clin Exptal Neuropsychol 1993(in press).

31 Damasio AR, Tranel D. Knowing that "Colorado" goeswith "Denver" does not imply knowledge that"Denver" is in "Colorado". Behav Brain Res 1990;40:193-200.

32 Tulving E. Remembering and knowing the past. Am Scient1989;77:361-7.

33 Iwai E, Mishkin M. Two visual foci in the temporal lobeof monkey. Japan-United States Joint Seminar onNeurophysiological Basis ofLearning, 1969.

34 Sakai K, Miyashita Y. Neural organization for the long-term memory of paired associates. Nature 1992;354:152-155.

35 Fuster JQ. 7he prefrontal cortex. Anatomy, physiology andneuropsychology, 2nd ed. New York: Raven Press, 1989.

36 Markowitsch HJ. Anatomical and functional organizationof the primate prefrontal cortical system. In: SteklisHD, Erwin J, eds. Comparative primate biology, vol IV.Neurosciences. New York: Alan R. Liss, 1988;99-153.

37 Stuss DT, Benson DF. The frontal lobes. New York: RavenPress, 1986.

38 Markowitsch HJ. Neuropsychologie des Gedachtnisses.Gottingen: Hogrefe, 1992.

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