Epilepsia, 47(3):615–625, 2006Blackwell Publishing, Inc.C© 2006 International League Against Epilepsy

Effects of Temporal Lobe Epilepsy on Retrograde Memory

∗†Suncica Lah, ‡Teresa Lee, §Sandra Grayson, and †‖Laurie Miller

∗Macquarie University, †University of Sydney, ‡Prince of Wales Hospital, §Westmead Hospital, and ‖Royal Prince AlfredHospital, Sydney Australia

Summary: Purpose: In a previous investigation (Lah et al.,2004), we found deficits in retrograde memory in patients whohad undergone temporal lobectomy (TL). In this study, we setout to determine whether such deficits are present before surgeryin patients with temporal lobe epilepsy (TLE).

Methods: Memory for public and autobiographic facts andevents was assessed in patients with focal left-sided (n = 15)or right-sided (n = 14) TLE and healthy control subjects (n =15). The impact of epilepsy and underlying cognitive deficits onretrograde memory also was examined.

Results: Patients with left TLE demonstrated retrograde mem-ory deficits across domains. Patients with right TLE showed de-fective recall only in the autobiographic domain. Young age atonset (younger than 14 years) was associated with greater dif-

ficulties in recall of famous events, and patients receiving poly-therapy had significantly reduced recall of autobiographic eventscompared with those receiving monotherapy. In most cases, de-ficient memory for the past was associated with impairments inother cognitive skills, especially language abilities.

Conclusions: In unoperated-on patients with TLE, we founddeficits in retrograde memory that were similar to those seen afterTL, with the pattern of deficits being influenced by side of le-sion, anticonvulsant medication, and word-finding deficits. Un-like patients tested after right TL, patients with right TLE did nothave difficulty recalling details of famous events, which raisesthe possibility that right TL results in a decline in this aspectof retrograde memory. Key Words: Retrograde memory—Autobiographic memory.

Studies examining retrograde memory in patients whohave undergone temporal lobectomy (TL) for intractableepilepsy have shown temporally extensive deficits on arange of retrograde memory tests (1,2). Kapur (3) arguedthat patients with epilepsy might have poor memory for thepast because seizures affect memory storage in a varietyof ways. He proposed that major seizures are likely to re-sult in a period of retrograde amnesia. Even minor seizuresmay have a cumulative effect over time and result in a pro-longed period of retrograde amnesia. Thus a longer historyof seizures and possibly a history of generalized tonic–clonic seizures would result in poorer retention of oldmemories and greater impairments on retrograde memorytests. Interestingly, however, in a previous study, we foundthat performance on retrograde memory tests after TL wasnot related to age at onset, duration of seizure disorder,or a history of generalized tonic–clonic seizures (2). Wedid find that patients who were still taking anticonvulsantmedications showed greater impairment than those whowere medication free. It seemed possible that the impactof a TL might outweigh effects related to seizure history.

Accepted September 23, 2005.Address corresponding and reprint requests to Dr. S.S. Lah at School

of Psychology, Mungo Mac Callum Building, The University of Sydney,Sydney NSW 2006, Australia. E-mail: sunnyl@psych.usyd.edu.au

To address this question, in this study, we sought to exam-ine remote memory and its relation to seizure variables inunoperated-on, temporal lobe epilepsy (TLE) patients.

In patients who have undergone TL, laterality of lesionhas been found to play a significant role in determiningpattern of retrograde memory impairment. Left temporallobectomy (LTL) has been associated with defective mem-ory for famous names and world events, whereas right TL(RTL) seems to impair recall of event details in both au-tobiographic and public domains, but to spare recall offamous names as well as memory for autobiographic se-mantic details (1,2,4).

In other types of patients, retrograde memory deficitshave been found to be associated with cognitive impair-ments in other domains including anterograde memory(5–7) and executive functioning (8–11). For TL patients,we found that underlying deficits in object naming andfluency contributed to the deficits on retrograde memorytasks (2). However, we found little correlation betweenretrograde and anterograde memory and no correlationbetween retrograde memory and other aspects of exec-utive functioning. Again, we wondered about the poten-tial impact of lobectomy on these relations, because thelikelihood of a risk of a decrease in verbal anterogradememory after LTL is well recognized (12–19), and reduc-tions of language-based skills such as naming and fluency

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616 S. LAH ET AL.

also have been reported (20–24). Hence it may be thatrelations between retrograde memory and other cognitiveskills change as a consequence of the surgery and thatthese relations may be stronger preoperatively.

The role of the mesial temporal structures in retrogradememory has been debated. Whereas the Standard Modelof Consolidation (SMC) (25) proposes temporally limitedhippocampal involvement, the recently developed Multi-ple Trace Theory (MTT) (26,27) posits the hippocampushaving a lifetime role in the retrieval of episodic autobio-graphic memories. Both theories agree that the neocorticalstructures are also essential for remote memories (se-mantic and episodic) and that semantic memories be-come independent of mesial temporal structures over time.Although some neuroimaging studies (28–31) showedinvariant hippocampal activation (as suggested by theMTT), one recent study revealed differential increases inhippocampal activation in retrieval of recent comparedwith remote autobiographic event memories (consistentwith the SMC) (32). Moreover, one study found a later-ality effect with respect to temporal involvement (33); adecrease in the activity of the right hippocampus for moreremote memories, and an invariant level of activity of theleft hippocampus in retrieval of autobiographic memoriesfrom across the life span. In addition, the neuroimagingstudies confirmed the involvement of various neocorticalregions. In our previous study, we found no evidence of atemporal gradient or laterality-of-lesion effect in memoryfor autobiographic events in patients who underwent TL(which is consistent with the MTT) but have wonderedwhether and to what extent this finding has been influ-enced by the surgery, as a standard temporal lobectomyalso includes not only mesial, but also anterolateral tem-poral regions.

Only two previous articles have addressed some ofthese issues in unoperated-on patients with focal epilepsy.Bergin et al. (34) used a multiple-choice questionnaire as-sessing knowledge of public events that had occurred overthe past decade. They found that a temporal lobe focus,history of frequent generalized convulsions, and impairedanterograde verbal memory were associated with poormemory for past public events. Bergin and colleagues (34)found no relation between age at seizure onset and perfor-mance on the memory questionnaire, although it should benoted that in their study, the onset of seizure disorder was>10 years earlier for all subjects, so that all would havebeen having seizures during the decade for which eventknowledge was being assessed. Finally, unlike the find-ings in postoperative patients, Bergin et al. noted no sideof lesion effects, with both the left temporal lobe epilepsy(LTLE) and right temporal lobe epilepsy (RTLE) patientsscoring poorly. Similarly, Viskontas et al. (4) found noeffects of age at seizure onset or laterality of seizure fo-cus on autobiographic-event memory in relatively smallgroups of preoperative TLE patients (five LTLE and eight

RTLE) by using only one measure of retrograde mem-ory, the Autobiographical Memory Interview (AMI) (35).This measure has been criticized as being insensitive tomilder retrograde memory deficiencies (36,37). Fluencymeasures have been proposed as being more sensitive toretrograde memory impairment (38) and have proven ableto detect such deficits in patients with Alzheimer dementia(9,39). They show correlations with as well as the samefactorial structure as other tests of autobiographic memorysuch as the AMI (9), but have never been used with TLEpatients. Moreover, neither Bergin et al. (34) nor Viskontaset al. (4) considered the possible impact of anticonvulsantmedications or deficits in related cognitive domains.

In this study, we set out to investigate the extent andpattern of retrograde memory deficits in patients with left-and right-sided TLE, by using a variety of assessment mea-sures that tapped autobiographic as well as public worldknowledge for the whole of the patient’s life. We consid-ered the possible influence of seizure variables and theimpact of other cognitive deficits on retrograde memoryin these patients.

METHODS

Subjects

PatientsPatients who were candidates for unilateral temporal

lobectomy at Royal Prince Alfred Hospital, WestmeadHospital, or Prince of Wales Hospital, Sydney, were con-sidered for this study. The study was approved by EthicsCommittees at all three hospitals, and all subjects gave in-formed consent. Only patients who were fluent in Englishand who were diagnosed with unilateral TLE by a treatingneurologist on the basis of clinical and neurophysiologi-cal information (including MRI and video-EEG monitor-ing) were eligible for inclusion. Patients were excluded ifthe following were found: a history of psychotic illness,cerebral pathology outside the temporal region, history ofneurologic disorders other then seizures, or an estimatedWAIS-R FSIQ <80 as determined by either the NART(40) or the WAIS-R Short Form (41).

The participants included 29 patients with TLE (14right and 15 left). In the RTLE group, the patients wereright-handed, except for two who were ambidextrous anddemonstrated left-hemisphere dominance for language inthe intracarotid sodium amytal (Wada) test. In the LTLEgroup, the patients were right-handed, except for onewho demonstrated bilateral language representation in theWada test. This patient’s results fell within the limits setby other LTLE patients, and thus her data were includedin the analyses. Many of these patients went on to havetemporal lobectomies, but for this study, all the patientswere tested before surgery. It may be important to notethat none of these patients were the same as those testedfor the postoperative studies previously reported (2).

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MEMORY IN TEMPORAL LOBE EPILEPSY 617

Seizure history was obtained through interviews andreview of hospital notes for all patients (Table 1). Thetwo patient groups did not differ significantly in the meanage at onset or duration of seizure disorder. Complex par-tial seizures represented the most common seizure type.Generalized tonic–clonic seizures were infrequent but hadbeen experienced at least once by 12 LTLE and nine RTLEpatients. χ2 analysis indicated no significant differencesin distribution in the two groups with respect to history ofgeneralized motor seizures. Details concerning hippocam-pal status were obtained from the MRI reports and, in pa-tients who underwent surgery, confirmed by pathology.They showed hippocampal pathology in 14 of 15 LTLEand 12 of 14 RTLE patients.

As can be seen in Table 1, patients with RTLE averagedmore seizures in the past year than did patients with LTLE;however, a good deal of variability was noted, and thebetween-group difference did not reach significance [F(1,27) = 2.62; p = 0.12]. All patients were taking medicationat the time of testing, with 76% (11 LTLE and 11 RTLE)taking more than one anticonvulsant (AED). The groupswere well matched on the mean number of AEDs.

Control groupFifteen normal control (NC) subjects were recruited to

match the patients on the basis of age, education, and sexdistribution. Subjects were included in the NC group onlyif they had no history of psychotic illness, head injury,or other neurologic disorders and their estimated WAIS-R FSIQ was >80. The majority of the NC subjects wererelatives or friends of the patients. The control group isthe same as that reported previously (2).

One-way analyses of variance revealed no significantdifferences between the three groups in age, education, orestimated FSIQ. χ2 analysis indicated no difference in sexdistribution between the different groups (see Table 1).

Materials

The Australian Remote Memory Battery (ARMB)This is a recently developed test designed specifically

for the Australian population (42). It comprises a Famous

TABLE 1. Clinical and demographic characteristics (means and range) of the sample

Group

LTLE (n = 15) RTLE (n = 14) NC (n = 15)

Onset age (yr) 18.1 (1–57) 26.6 (1–48)Duration of epilepsy (yr) 19.9 (1–48) 16.1 (1–56)No. of seizures in last year 80.3 (2–365) 170.8 (2–700)No. of AEDs 1.9 (1–3) 1.9 (1–3)Age (yr) 37.8 (20–57) 42.7 (21–60) 36.3 (23–53)Education (yr) 11.9 (9–16) 11.6 (8–16) 12.7 (7–16)Estimated FSIQ 100.4 (86–118) 103.5 (91–115) 105.9 (86–115)Sex M/F 4/11 8/6 6/9

The onset age was the age at which an ongoing seizure disorder began.LTLE, left temporal lobe epilepsy; RTLE, right temporal lobe epilepsy; NC, normal control; AED, antiepileptic drug.

Faces and Public Events Test. Most of the faces are Aus-tralian, and most of the Public Events questions are relatedto famous events that occurred in Australia; however, someitems concern international personalities or events. TheFamous Faces Test consists of 63 (15 × 20-cm) black-and-white photographs of famous people to be named, and theFamous Events Test has 63 questions about famous publicevents (“What was the Granville disaster that occurred in1977?”). Each test contains items from different domainsof public life (sports, politics, entertainment) spreadingover seven decades (nine items per decade), and in twoconditions: free recall and forced (three-choice) recogni-tion. Free recall is always administered first, with recog-nition choices presented immediately afterward for eachitem. Items are presented in a pseudo-random order, withitems from each decade and domain of public life spreadover the whole series. The total number of correct an-swers/choices served as the score for the recall/recognitioncondition. In this study, we analyzed results from itemspertaining only to the last three decades (1970s to 1990s),as this sampled the adult life of most subjects.

The Public Fluency Test (PFT)

The PFT is a newly developed task that parallels seman-tic tasks used by Dritschel et al. (38). The PFT has two con-ditions; fluency for famous names (PFT-Names) and flu-ency for famous events (PFT-Events). In the PFT-Names,subjects are asked to generate names of famous peoplefrom different domains of public life (i.e., sports, politics,and entertainment) and are given 90 s for each category.The total number of names from the three domains is takenas the score. In the PFT–Events, subjects are asked to re-call public events that took place during their lifetimes.They are instructed that they do not need to recall detailsof the events; however, the answer has to provide suffi-cient information to specify a particular type of event (e.g.,“Vietnam War” rather than “a war overseas”) to be givena credit. A total of 90 s is allotted for generating PublicEvents.

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618 S. LAH ET AL.

The Autobiographical Fluency Test (AFT)The AFT also is based on a task developed by Dritschel

et al. (38). It has two conditions: friends’ names (AFT-Names) and personal events (AFT-Events). In our ver-sion of the AFT-Names, a subject is given 90 s each torecall names of friends or acquaintances from differentlife periods: preschool, primary school, high school, the5 years after high school, and the most recent 5 years.An average score is then obtained for each subject forthe childhood years (preschool and primary school years),teenage years/young adulthood (high school and 5 yearsafter high school), and this is compared with the scorefor the most recent 5 years. To be given credit, differentfriends/acquaintances must be recalled in different peri-ods (i.e., the same friend’s name is not given credit if itwas generated in a second time period). Only the firstname or the family name is sufficient to be given credit.In the AFT-Events, subjects are asked to generate per-sonal events from the same life periods discussed earlier.Again an average score for each of the three life periods isobtained. Subjects are informed that they do not need torecall details of an event and are encouraged to report onan event even if they had only a vague recollection of it.In many cases, points are awarded on this measure for therecall of recurrent events (i.e., “walking to school with afriend”) as well as individual ones (e.g., breaking my legwhile walking to school). Fluency for names and eventswas always tested in the same way, from earliest to mostrecent life period.

Other cognitive skillsAnterograde verbal memory was assessed by using the

raw score from the 30-min delayed recall of the WMS-R Anna Thompson Story (43). Anterograde visual mem-ory tests composed a 30-min delayed recall of the Rey-Osterreith Complex Figure (RCFT) (44,45), which wasscored according to the Taylor criteria (46), and FamilyPictures from the WMS-III (47). On this last task, subjectsare asked to recall details of complex visual scenes 30 minafter studying them. The age-scaled score was used fromthis measure.

Object-naming ability was assessed by using the BostonNaming Test (BNT) (48). From this test, we used the totalnumber of words generated spontaneously in response tothe line drawings.

Semantic and phonologic verbal fluency were assessedby using Animal Fluency (49) and the Controlled OralWord Association Test (COWAT) (50,51), respectively.The total number of animals given in 1 min and the totalnumber of correct words starting with F, A, and S (1 mineach) served as the scores.

Tests of working memory, inhibition, and mental flex-ibility were the Digit Span subtest from the WAIS-R(43) (digit span backward), Stroop Test (52) (inhibition

T score), and Trail-Making Test (TMT) (53) [(Trail B time– Trail A time)/Trail A time].

ProcedureAll subjects were administered tests assessing their abil-

ity to remember events and people from public and auto-biographic domains by the main investigator (S.L.) in onesession. The remote memory tests were always adminis-tered in the following order: The AFT (Fluency for Names,Fluency for Events), the PFT (Fluency for Names, Fluencyfor Events), and the ARMB (Famous Faces Test, FamousEvents Test). The ARMB was used only with subjects wholived in Australia during the decades sampled because ofthe strong cultural bias. All TLE and 12 NC subjects wereadministered the ARMB.

Administration of the standardized tests of other cog-nitive abilities was conducted mainly by clinicians (S.G.,T.L., or L.M.) as a part of a routine presurgical neuropsy-chological assessment. If any of these had not been in-cluded in the clinical protocol, it was administered in thesame session as the retrograde memory tests. The stan-dardized neuropsychological tests were always adminis-tered before the retrograde memory tests. Control subjectswere administered the complete battery of tests in the samesession (with some breaks) by S.L.

Statistical analysesThe expectation maximization algorithm (54) was used

to make estimates of missing data for two control subjectswho declined to reminisce about autobiographic eventsfor periods of their life because of painful memories (totalof three periods for two subjects).

All scores were found to be normally distributed.Between-group differences on tests of retrograde mem-ory and other cognitive skills were evaluated by usingeither two-way (Group × Time Period) repeated measureanalyses or one-way analyses of variance (ANOVAs) andSheffe’s post hoc tests. All comparisons that were signif-icant at the p < 0.05 level are reported.

For the patients, relations between retrograde memory,other cognitive skills, and epilepsy variables were calcu-lated by using the Pearson correlation coefficient r. Onlythose remote memory and cognitive variables that showedsignificant between-group differences were entered intothe correlational analyses. Given the large number of cor-relations tested and the relatively small sample size, a moreconservative p value of 0.025 instead of 0.05 was used toreduce the likelihood of type I error.

Finally, a series of analyses of covariance (ANCOVAs)was undertaken to determine whether the between-groupdifferences in retrograde memory could be explained byunderlying differences in other cognitive areas. Standard-ized cognitive measures that correlated significantly witheach of the retrograde memory measures were used ascovariates.

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FIG. 1. Australian Remote Memory Battery, Famous Faces Test–Recall (Face Recall) and Recognition (Face Recog) Conditions,Famous Events Test–Recall (Event Recall) and Recognition(Event Recog) Conditions: mean number of correct responsesfor normal control (NC), right temporal epilepsy (RTLE) and lefttemporal lobe epilepsy (LTLE) groups. ∗∗, p < 0.01.

RESULTS

Effects of side of lesion

The Australian Remote Memory Battery (ARMB)Figure 1 presents the results obtained on this test bat-

tery. Analyses of the ARMB Famous Faces Test–RecallCondition showed no Group × Time Period interaction buta significant main effect of Group [F(2, 38) = 8.75; p <

0.002] when collapsed across time periods. Scheffe’s posthoc tests showed that the LTLE group named significantlyfewer famous faces compared with the NC (p < 0.001)group. On the ARMB Famous Faces Test–RecognitionCondition, analyses yielded no interaction and no main ef-fect of Group. For the ARMB Famous Events Test–RecallCondition, a significant main effect of Group [F(2, 38) =9.55; p < 0.001] was found, but no interaction. Post hoctests showed that the LTLE group recalled significantlyfewer details about famous events compared with the NC(p < 0.001) and RTLE (p < 0.04) groups. Analyses ofthe ARMB Famous Events Test–Recognition Condition(see Fig. 1) again yielded a main effect of Group [F(2, 38)= 9.55; p < 0.001] and no interaction. Post hoc analysesshowed that even in this condition in which answers werepresented among distractors, the LTLE group performedmore poorly than the NC (p = 0.001) and RTLE (p < 0.02)groups.

The Public Fluency Test (PFT)Results on the PFT are shown in Fig. 2. The between-

group differences were significant for both conditions:PFT-Names [F(2, 41) = 5.64; p < 0.01] and PFT-Events[F(2, 41) = 7.45; p < 0.005]. Post hoc analyses showedthat on both PFT-Names and PFT-Events, the LTLE (butnot the RTLE) generated significantly fewer responsesthan the NC group (p < 0.01 and p < 0.005, respectively).The LTLE and RTLE groups did not differ significantly.

FIG. 2. Public Fluency Test (PFT)–Names and Events: meannumber of items generated by normal control (NC), right tempo-ral lobe epilepsy (RTLE), and left temporal lobe epilepsy (LTLE)groups. For Names, the score is the total from three categories(politics, sport, and entertainment) with 90 s each, whereas theEvent score is from one 90-s interval. ∗∗p < 0.01.

Autobiographical Fluency Test (AFT)Results from the AFT are presented in Fig. 3. Neither

the AFT-Names nor AFT-Events analyses revealed a sig-nificant Group×Time Period interaction, but both showeda significant main effect of Group [F(2, 41) = 8.46; p <

0.002 and F(2, 41) = 4.24; p < 0.03, respectively]. Whencollapsed across the time periods sampled, post hoc anal-yses showed that on the AFT-Names, both the LTLE andRTLE groups generated fewer names of friends and ac-quaintances compared with the NC group (p < 0.02 forboth). On the AFT-Events, only the RTLE group gener-ated significantly fewer autobiographic events than the NCgroup (p < 0.05). The LTLE group also performed belowthe NC mean, but the between-group difference just failedto reach significance (p = 0.07).

Relations between seizure variables and memory forthe past

Group differencesPatients with early seizure onset (N = 10; younger than

14 years) obtained lower mean scores on all retrogradememory measures, across the time periods. The between-group difference (Early Onset vs. Late Onset), reached

FIG. 3. Autobiographical Fluency Test (AFT)–Names and Events:mean number of autobiographically relevant items generated bynormal control (NC), right temporal lobe epilepsy (RTLE), and lefttemporal lobe epilepsy (LTLE) groups.∗p < 0.05.

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620 S. LAH ET AL.

FIG. 4. Mean scores obtained by earlyseizure onset (younger than 14 years)and late seizure onset (older than 14years) groups on the Australian Re-mote Memory Battery, Famous FacesTest–Recall (ARMB Face Recall) andRecognition (ARMB Face Recog.), Fa-mous Events Test–Recall (ARMB EventRecall) and Recognition (ARMB EventRecog.); Public Fluency Test–Names(PFT Names) and Events (PFT Events);Autobiographical Fluency Test–Names(AFT Names) and Events (AFT Events).∗∗p < 0.01.

significance for the ARMB–Famous Events Recall [F(1,27) = 8.20; p < 0.01] and Famous Events Recognition[F(1, 27) = 10.56; p < 0.005], as can be seen in Fig. 4.

Complex partial seizures represented the most commonseizure type, experienced by 75% of the patients, usu-ally accompanied by infrequent generalized tonic clonicseizures (55%). Generalized tonic–clonic seizures werethe only seizure type in 25% of the patients. The differ-ence between the patients who experienced generalizedtonic–clonic seizures (in combination with complex par-tial seizures or on their own) compared with patients whoexperienced only complex partial seizures did not reachstatistical significance for any retrograde memory score.

Patients who were receiving polytherapy obtainedlower results on all retrograde memory measures exceptfor ARMB–Famous Faces Test Recall compared with pa-tients who were receiving monotherapy. Nevertheless, thedifference between the polytherapy and monotherapy pa-tient groups reached significance on only one retrogradememory measure: AFT-Events [F(1, 27) = 17.83; p <

0.05] (see Fig. 5). None of the Group (Polytherapy vs.

FIG. 5. Mean scores obtained by monotherapy and polytherapygroups on the Australian Remote Memory Battery, Famous FacesTest–Recall (ARMB Face Recall) and Recognition (ARMB FaceRecog.), Famous Events Test–Recall (ARMB Event Recall) andRecognition (ARMB Event Recog.); Public Fluency Test–Names(PFT Names) and Events (PFT Events); Autobiographical FluencyTest–Names (AFT Names) and Events (AFT Events). ∗∗p < 0.05.

Monotherapy) × Time Period interactions was signifi-cant.

Correlation analysesAs can be seen in Table 2, none of the correlations be-

tween duration of epilepsy disorder or number of seizuresexperienced in the last year and retrograde memory mea-sures reached significance. Consistent with the findingsfor the group analyses, the correlations between onset ageand ARMB Event Recall and Recognition were signifi-cant, and a negative correlation also was noted betweenthe number of AEDs and the AFT-Events score. In addi-tion, a significant negative correlation was found betweena number of AEDs and the ARMB–Famous Event Recog-nition score.

Other cognitive variables

Group differencesBetween-group differences in cognitive variables other

than retrograde memory are outlined in Table 3. Deficitsin anterograde memory were frequent; compared with theNC group, both the LTLE and RTLE groups were impairedon a delayed story recall (p < 0.05) and delayed recall ofcomplex visual scenes (Family Pictures) (p < 0.01). TheRTLE group recalled a significantly smaller number ofvisual details of the RCFT compared with the NC group(p < 0.01).

Spontaneous confrontational naming (BNT) was im-paired in the LTLE compared with the NC and RTLEgroups (p < 0.05). Significant between-group differencesalso were obtained on semantic (Animal) fluency andphonologic fluency (COWAT) tests; only the LTLE groupwas impaired on semantic fluency relative to the NC group(p < 0.01), but both patient groups were impaired rela-tive to NC subjects on the phonologic fluency test (p <

0.01). Groups did not differ significantly on measures ofworking memory, inhibition, or mental flexibility, as mea-sured by the Digit Span, Stroop, or Trail Making tests,respectively.

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TABLE 2. Correlation coefficients between retrograde memory and epilepsy variables for patients with temporal lobe epilepsy

Public Fluency Test Autobiographical Fluency TestAustralian Remote Memory Battery

Famous Face Famous Event Famous EventRecall Recall Recognition Names Events Names Events

Onset age 0.16 0.43a 0.55 a 0.18 0.16 0.09 0.19Duration of epilepsy −0.17 −0.22 −0.27 −0.25 −0.19 −0.15 −0.10

No. of antiepileptic drugs −0.11 −0.32 −0.42b −0.18 −0.25 −0.18 −0.52a

No. of seizures in last year 0.02 0.18 0.12 −0.08 0.10 −0.01 −0.01

Significance levels: ap < 0.01; bp < 0.025.

Correlational analysesAll retrograde memory and all other cognitive tests that

revealed group differences were included in the correla-tional analyses. Results of the analyses are presented inTable 4. Numerous significant correlations were foundbetween tests of anterograde and retrograde memory.Furthermore, object-naming test scores (BNT) and perfor-mance on tests of remote memory correlated in most in-stances. Not surprisingly, semantic (Animal) fluency cor-related significantly with performance on the retrogradefluency tests for names (PFT-Names and AFT-Names),but it also correlated with the ability to recall details offamous events in response to a specific question (ARMB–Famous Events Test–Recall). And finally, phonologic flu-ency (COWAT) correlated significantly with all remotememory tests, except for the ability to generate events fromone’s own past (AFT–Events). Of the retrograde memorymeasures, only fluency for autobiographic events provedto be unrelated to any of the cognitive variables that re-vealed significant between-group differences.

Impact of other cognitive variables on retrogradememory: ANCOVA results

When one or more of cognitive variables that were sig-nificantly correlated with retrograde memory measures

TABLE 3. Mean scores (standard deviations) for the left temporal lobe epilepsy (LTLE), right temporal lobeepilepsy (RTLE) and normal control (NC) groups on tests of anterograde memory, object naming and executive

functioning.

Group

Measure LTLE RTLE NC F

Story: delayed recall (RS) 8.1 (5.9) ‡ 8.5 (3.9) ‡ 13.5 (4.9) 5.49a

RCFT: delayed recall (RS) 15.1 (5.9) 13.6 (4.4) �= 20.3 (6.5) 5.37a

FP: delayed recall (SS) 6.0 (2.9) ‡ 5.5 (2.3) ‡ 8.7 (2.8) 5.93a

BNT: no. spontaneously named 46.1 (7.2)′ ′ 52.8 (6.8) 53.5 (4.6) 5.96a

Animal Fluency (RS) 15.7 (4.6) † 18.9 (5.8) 22.2 (5.5) 5.69a

COWAT (total RS for 3 letters) 24.7 (8.8) ‡ 31.4 (8.9) ‡ 44.8 (9.6) 18.17a

Digit Span–backward (RS) 6.3 (1.8) 7.0 (2.4) 5.6 (1.1) 2.16Stroop–inhibition (T score) 56.8 (10.2) 52.5 (4.9) 53.1 (9.2) 0.83TMT: B-A/A (s) 1.4 (.8) 1.8 (.8) 1.3 (.6) 1.79

RS, raw score; RCF, Rey-Osterreith Complex Figure (31,32); FP, Family Pictures subtest from the Wechsler Memory Scale,3rd ed. (34); SS, scaled score; BNT, Boston Naming Test (35); COWAT, Controlled Oral Word Association Test (37,38); TMT,Trail-Making Test (40).

ap < 0.01.Post hoc results: ‡, LTL & RTL<NC; �=, RTL<NC; ′ ′, LTL < RTL; †, LTL<NC.

were used as covariates in the ANCOVAs, differences be-tween the LTLE, RTLE, and NC groups no longer reachedsignificance for any retrograde memory measures, exceptAFT–Events (which did not correlate significantly withany of the cognitive variables). Similarly, the finding ofgreater impairment of the polytherapy group on this mea-sure compared with the monotherapy group was not ex-plained by differences on other cognitive variables,

Results of the ANCOVAs suggest that among cognitivevariables, performance on object naming (Boston Nam-ing Test) alone was sufficient to explain the between-group differences on several retrograde memory mea-sures (ARMB Famous Faces Recall, ARMB FamousEvents Recall, ARMB Famous Events Recognition andPFT-Names). The between-group differences on the PFT-Names could also be accounted for by phonologic(COWAT) or semantic (Animal) fluency alone. In con-trast, ANCOVAs that used anterograde memory measuresas individual covariates continued to yield between-groupdifferences on the retrograde measures, indicating that an-terograde memory alone was not sufficient to explain ret-rograde memory performance. A combination of phono-logic fluency (COWAT) and anterograde verbal memorywas sufficient to eliminate between-group differences onPFT–Events and AFT–Names.

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TABLE 4. Correlation coefficients between retrograde memory, anterograde memory, naming, and executive skills for patients withtemporal lobe epilepsy

Public Fluency Test Autobiographical Fluency TestAustralian Remote Memory Battery

Famous Face Famous Event Famous EventRecall Recall Recognition Names Events Names Events

Story–delayed 0.38a 0.36a 0.32 0.34 0.35a .48b .36RCF–delayed 0.32 0.22 0.18 0.28 0.20 0.26 .00FP–delayed 0.36a 0.33 0.27 0.33 0.29 .39a .40

BNT 0.62b 0.58b 0.63b 0.44b 0.26 .36a .25

Animal Fluency 0.30 0.37a 0.34 0.45 b 0.29 .36a −.29

COWAT 0.39a 0.51b 0.46b 0.50b 0.39b .59a .31

RCF, Rey-Osterreith Complex Figure (31,32); FP, Family Pictures subtest from the Wechsler Memory Scale–3rd ed. (34); BNT, Boston NamingTest (35); COWAT, Controlled Oral Word Association Test (37,38).

ap < 0.025.bp < 0.01.

The difference between Early Onset versus Late Onsetgroups in recall and recognition of public event details(ARMB–Event Recall and ARMB–Event Recognition)remained significant when the relevant other cognitivevariables were included in the ANCOVA.

DISCUSSION

This study revealed temporally pervasive memorydeficits and strong side-of-lesion effects in unoperated-on patients with TLE. Patients with LTLE were sig-nificantly impaired on almost all tests of past memory,including measures of both public and autobiographicmemory. The RTLE group, conversely, showed impair-ments in recall of autobiographic information only. Earlyage at onset (younger than 14 years) and polytherapy had asignificant negative impact on recognition of public eventdetails and recall of autobiographic events, respectively.No other epilepsy variables (e.g., history of generalizedtonic–clonic seizures, duration of epilepsy disorder, cur-rent seizure frequency) seemed to influence retrogradememory performance.

Patients also performed poorly on tests of anterogradememory, object naming, semantic fluency, and phonologicfluency, and, in many instances, scores on these standardclinical tests correlated with scores on the retrograde mem-ory measures. Further analyses showed that although noneof the anterograde memory measures could account for thebetween-group differences in retrograde memory, perfor-mance on the measures of language abilities and executivefunctioning proved to be important.

Similar to patients NT (55) and HM (56) with lim-ited mesial temporal lobe damage, our patients’ retrogradememory difficulties were temporally pervasive. This lackof temporal gradient in episodic autobiographic memoryretrieval may be seen as supportive of the MTT (26,27),which proposes that mesial temporal structures have a life-long role in retrieval of retrograde memories. Neverthe-less, the fact that no temporal gradient was obtained intasks that require retrieval of semantic information raises

concerns that variables in addition to the effect of a hip-pocampal lesion/seizure focus are having an influence onretrograde memory.

For example, it has been suggested that temporal lobeseizures interfere with a long-term consolidation process(3,57) and have a cumulative effect on retrograde memory(58). Jokeit et al. (59) assessed 24-h retention of newlylearned materials in patients with unilateral refractoryepilepsy during long-term video-EEG monitoring. Theyfound that patients with LTLE who experienced a seizureduring the 24-h retention interval had defective retentionof newly learned materials compared with the LTLE pa-tients who were seizure free during the same period. Fur-thermore, studies of patients with TLE who complainedof memory deficits but performed at or near normal levelon traditional anterograde memory tests (including re-call of material after a short delay) did indeed show im-paired recall of the same materials when tested weeks ormonths later compared with normal control subjects (60–64). Therefore one might expect that earlier onset/longerduration of epilepsy would result in more-extensive am-nesia for past events because of a poor ability to consoli-date new memories. In spite of a good range of values onvariables such as age at onset and years of seizures in ourstudy, however, we found only limited evidence of a cumu-lative effect of seizures on retrograde memory. We foundno significant correlations between duration of epilepsyand performance on the retrograde memory tasks. In onlytwo instances (i.e., recall and recognition of public eventsdetails), did patients with early onset obtain significantlylower scores than those of patients with late onset. In addi-tion, although for many of our patients, the earliest periodtapped by the memory measures would predate the onsetof their seizure disorder, we found no significant Group ×Time Period interactions to suggest relative sparing of veryearly memories. This indicates that the onset of a seizuredisorder interfered with stored memories (i.e., for eventsand people that were encountered years before the onsetof seizures) and did not just interfere with new memoryconsolidation.

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Further evidence of impaired long-term memory storescomes from our findings for Public Event memory;between-group differences were found both in the recalland recognition of famous events’ details. This suggeststhat the patients’ poor ability to answer questions pertain-ing to past events was the result of impoverished knowl-edge stores rather than simply impaired retrieval. Earlyonset of epilepsy was associated with deficient memoryfor public events. This suggests either that some disrup-tion to the brain’s ability to organize these sorts of memo-ries is present when seizures occur at a young age or thatthe underlying pathology is responsible for both an earlyseizure onset and a poor ability to retain knowledge ofpublic events.

Our findings in this study and the previous one (2) sug-gest that AEDs have a significant impact on retrogradememory. In this study, a consistent trend of lower retro-grade memory scores was achieved by patients who werereceiving polytherapy compared with patients receivingmonotherapy, and this difference reached significance forthe retrieval of autobiographic events. In our previousstudy of postoperative patients, those who were still takingAEDs consistently performed worse than those who weremedication free. Obviously it will be important in futurestudies to consider how medication affects the ability toremember the past.

The relation between language skills and retrogradememory in patients with TLE or TL has not previouslybeen explored. The relation between language abilities andanterograde memory, however, has been debated for sometime. Stage-of-processing theories (65–67) suggest thatlanguage and memory use completely separate brain unitsand processes that are sequentially organized. Accordingto these theories, the hippocampus is thought to have apivotal role for memory, but not language. Distributed-memory theories, conversely, propose that verbal mem-ory depends on the pattern and strength of connectionsbetween a very large number of neural units that are dis-tributed through a vast activation network and that are alsoimportant for language production (68–71). These con-clusions are based, in part, on findings from the patientH.M. (who had a bilateral mesial temporal lobe resec-tion); although most previous literature has emphasizedH.M.’s anterograde memory deficits (72,73), recent lan-guage studies (71,74) indicated that many of his languageskills are impaired and have been so since early 1970s.Davies et al. (20) were the first to report that pre- andpostoperative naming abilities in TL patients were asso-ciated with the pathologic status of hippocampus, whichled them to conclude, “. . .the hippocampus and its connec-tions may be directly involved in retrieval of names fromthe lexicon, providing access to cortical language areas”(p. 415). Our results support distributed-memory theories;we found that numerous significant correlations betweenmemory and language measures and differences in word-

finding abilities accounted for many between-group dif-ferences in memory for the past.

One of the few retrograde memory impairments thatcould not be explained on the basis of impairments inrelated cognitive variables was defective retrieval of auto-biographic events by the RTLE group. At first glance, thisfinding seems consistent with the proposal that right hemi-sphere is more important than the left for the recollectionof autobiographic events (75). Our results, however, donot offer strong support to this hypothesis because (a) thedifference between the RTLE and LTLE groups was notsignificant, and (b) the difference between the LTLE andNC groups just failed to reach significance. It also is im-portant to note that this deficit was not found for the RTLgroup in our previous study (2), and no side-of-lesion ef-fect was found in a second study of autobiographic eventmemory in combined groups of patients with TLE or tem-poral lobectomy (4). Further studies should help to clarifywhether the side-of-lesion effect found in the present studycan be substantiated.

Our finding of intact recall of famous events in theRTLE group is at odds with the result we obtained in ourstudy of postoperative TL patients (2). In that study, bothleft- and right-TL patients had difficulty on the famousevents test. This was the only measure on which postoper-ative patients as a group demonstrated a deficit that had notbeen detected in the preoperative sample. This raises thepossibility of a decline in memory for famous events afterright TL. Because the two studies used different subjects,however, we cannot be sure that the difference in patternof results is not simply the result of a sampling differ-ence. Several of the TLE patients in the present study havesince undergone surgery. We are currently reviewing thesepatients postoperatively and will be looking for signs ofdeterioration in their retrograde memory to examine thispossibility.

Acknowledgment: This research was in part supported bythe Research Scholarship awarded to the first author by the Aus-tralian Epilepsy Association. We thank the neurologists and neu-rosurgeons at RPA, Westmead, and POW hospitals for access tothe patients, Ms. Sally McSwiggin and Ms. Sarah Lucas for helpwith patient recruitment, and Dr. Alan Taylor for his assistancewith the statistical methods.

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