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Neuropsychologia 44 (2006) 2792–2805

How children suffering severe amnesic syndrome acquire new concepts?

Sylvie Martins a,b,c,d,e, Berengere Guillery-Girard a, Isabelle Jambaque b,Olivier Dulac c,d, Francis Eustache a,∗

a Inserm, EPHE, Universite de Caen, Unite E0218, GIP Cyceron, CHU Cote de Nacre, 14033 Caen Cedex, Franceb Universite Paris Descartes, Laboratoire Cognition et Comportement, CNRS.FRE-2987, Paris, France

c Inserm U663, Service de Neurologie et Metabolisme, Hopital Necker-Enfants Malades, Parisd Universite Paris Descartes, Necker, Paris, France

e Service Hospitalier Frederic Joliot, Departement de Recherche Medicale, CEA, Orsay, France

Received 2 March 2005; received in revised form 21 March 2006; accepted 21 May 2006Available online 25 July 2006

bstract

Recent studies revealed that children with developmental amnesia acquired new semantic information. However, they failed to investigate therowth of such knowledge during childhood, and they did not bring evidence concerning the putative role of residual episodic memory in semanticcquisition. This prospective study sought to clarify this issue by assessing both semantic and episodic memory in two amnesic children (RH andF) with different neuropsychological profiles. We thus applied errorless semantic learning and vanishing cues methods, together with assessmentsf episodic memory using original recognition tasks within the same protocol. Results demonstrated learning and long-lasting maintenance ofulticomponent concepts (comprising labels, categories and features) in both amnesic children. Importantly, episodic memory assessments revealed

ifferential residual abilities in these children, which may account for their respective profiles of semantic acquisition. Thus, RH, who demonstrated

esidual episodic abilities, acquired normally. However, the learning of KF, who had a massive impairment of episodic memory, remained slowerhan her controls. In conclusion, even though an episodic impairment may slacken new semantic learning, our research provides new evidence forhe de novo acquisition of semantic concepts in childhood amnesic syndrome and strengthens the idea that semantic learning can occur withoutny recruitment of episodic memory.

2006 Elsevier Ltd. All rights reserved.

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eywords: Concept learning; Amnesia; Child; Recollection; Episodic memory

. Introduction

Neuropsychology and functional imaging have markedlymproved our understanding of human memory and led to theevelopment of several hierarchical models. Among them is Tul-ing’s Serial–Parallel–Independent (SPI) model, which is basedn five types of memory, all closely linked (Tulving, 1995). Inarticular, Tulving distinguishes between episodic and semanticemory. Episodic memory is considered to be the most highly

eveloped form of memory in terms of phylogeny and ontogeny.t refers to “memory for personally experienced events” and

ncludes the “autonoetic awareness of one’s experiences inhe continuity of subjectively apprehended time that extendsoth backward into the past [. . .] and forward into the future”.

∗ Corresponding author. Tel.: +33 2 31 06 51 97; fax: +33 2 31 06 51 98.E-mail address: neuropsycho@chu-caen.fr (F. Eustache).

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028-3932/$ – see front matter © 2006 Elsevier Ltd. All rights reserved.oi:10.1016/j.neuropsychologia.2006.05.022

antic memory

emantic memory is regarded as “memory for general facts,”ssociated with “one’s noetic awareness of the existence of theorld and objects, events, or other regularities in it” (Tulving,001). According to this author, the hippocampus is necessaryor remembering ongoing life experience (i.e., episodic mem-ry), but not necessary for the acquisition of factual knowledgei.e., semantic memory), which can notably be mediated byhe surrounding mediotemporal structures (i.e., the entorhinal,erirhinal and parahippocampal cortex) (Tulving & Markowitsh,998). Conversely, Squire and colleagues propose that episodicnd semantic memory depend on declarative memory and oper-te in a parallel manner. Hence, episodic and semantic memoryay rely on a common neural network (i.e., the medial tem-

oral lobe and diencephalic regions). Consequently, a cerebral

esion in these structures may lead to a proportionate impair-

ent of both episodic and semantic memory (Squire & Zola,998). These two conceptions thus imply strongly differentssumptions in amnesic syndromes. The former predicts that

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S. Martins et al. / Neuropsy

ew information can be integrated into semantic memory with-ut being encoded in episodic memory, while the latter supposeshat any amnesic patient fails in new semantic acquisition.

Early research carried out with the famous patient HM ini-ially recorded global declarative disturbances leading to thessumption that both episodic and semantic memories werempaired in anterograde amnesia (Gabrieli, Cohen, & Corkin,988; Milner, 1959). Recent reports have extended this assump-ion to other amnesic patients (Bayley & Squire, 2004; Kitchener

Squire, 2000; Manns, Hopkins, & Squire, 2003). Yet, sev-ral studies have reported significant semantic learning in HMO’Kane, Kensinger, & Corkin, 2004), particularly when thisnformation could be linked to mental representations estab-ished preoperatively (Stokto et al., 2004). Otherwise, manyeports have highlighted that the “meaningfulness” of mate-ials and the frequency of exposure or rehearsal were criticaleterminants for amnesic patients to acquire (Rosenbaum et al.,005; Tulving, 2002; Westmacott & Moscovitch, 2001). Theseorks thus suggest that, in addition to the extent of patient’s

esions, previous failures to demonstrate new semantic learn-ng may result from nonoptimal teaching patterns and a lack ofreoperative mental representations on which amnesic patientsould build new associations (Bayley & Squire, 2004; Gabrielit al., 1988; Kitchener & Squire, 2000). Indeed, several studiesave showed that using appropriate learning methods (such asanishing cues technique and material relevant to the patient)llows amnesic patients to acquire relatively stable informationVan der Linden, Meulemans, & Lorrain, 1994; Van der Lindent al., 2001). For instance, Guillery et al. (2001) revealed thecquisition of novel semantic knowledge in three patients suf-ering from transient global amnesia by using sentences puzzles.

Against this idea of semantic learning preservation in amne-ia, Squire and Zola (1998) have voiced two main criticisms:1) This learning is slower and performances are poorer thanhose of controls, providing evidence for an objective seman-ic deficit (Bayley & Squire, 2004; Kitchener & Squire, 2000;quire, 1992; Manns et al., 2003). (2) Patients retain residualbilities in episodic memory, which is why their episodic per-ormance is above 0. Concerning the first criticism, Tulvingnd Markowitsh (1998) counter that this difference in seman-ic results can be explained by the fact that, contrary to patients,ealthy subjects can use their episodic memory to encode andetrieve novel semantic information, but also to limit interfer-nce generated by mistakes (Tulving, Hayman, & Macdonald,991). Regarding the second criticism, paradigms need to beeveloped in order to assess the precise role of episodic mem-ry in semantic acquisition. As traditional episodic memory testsllow the subject to succeed in recognition tasks thanks to aeeling of familiarity subserved by semantic memory and pre-erved in permanent amnesic syndrome, Tulving has proposedhe “Remember/Know paradigm” (R/K paradigm) to gauge thenvolvement of episodic and semantic memory respectively inecognition tasks (Tulving, 1995). Baddeley, Vargha-Khadem,

nd Mishkin (2001) have strengthened this point in one casef developmental amnesia, reporting that Jon’s impairment inree recall of unfamiliar newsreel events contrasted with a pre-erved ability to perform a recognition task suggesting that

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gia 44 (2006) 2792–2805 2793

he results did not reflect residual abilities in episodic mem-ry but rather were supported by a feeling of familiarity. In thisase, subsequent cerebral reorganization and the developmentf compensatory strategies may have contributed to the residualerformance on the recognition task. However, relatively littleesearch has been carried out in semantic memory in permanenthildhood amnesia.

In 1987, Ostergaard reported the case of CC, who had sus-ained hippocampal, parahippocampal and periventricular dam-ge due to an encephalopathy after intoxication when he was 10ears old. As he showed notably severe reading disabilities, theuthor postulated that both his episodic and semantic memoriesere impaired. Subsequent studies have suggested that episodic

apacities need to be preserved if novel semantic knowledge is toe acquired (Broman, Rose, Hotson, & MacCarthy-Casey, 1997;evin et al., 1996). However, Brizzolara, Casalini, Montanaro,nd Posteraro (2003) reported the opposite pattern of results inhe case of AV, who became amnesic at the age of 6, after anpisode of acute encephalopathy. Furthermore, these amnesichildren suffered from extensive lesions (including frontal, insu-ar, thalamic, hippocampal and temporal damages) preventinghe conclusion that there is a causal link between episodic dis-urbance and semantic memory deficiency but rather reveal arequent cooccurrence subserved by extensive cerebral networkysfunction. Finally, Vargha-Khadem and colleagues publishedajor works concerning children (ages 11–16) with permanent

mnesic syndrome resulting from lesion mostly restricted tohe hippocampus (Gadian et al., 2000; Vargha-Khadem et al.,997). Their overall intellectual efficiency was preserved, andheir level of comprehension, vocabulary and general knowledges well as their language abilities (reading and writing) werelose to those of age-matched healthy children. These studieshus tended to demonstrate that children can acquire seman-ic knowledge de novo despite severe episodic impairment. Allhese children’s case reports are relevant given that young chil-ren and preadolescents do not yet possess expert knowledgei.e., premorbid extensive semantic knowledge) to facilitate thentegration of new semantic information and because they min-mise the instrumental and executive functions involved in com-ensation strategies that become fully efficient in adulthood.onetheless, pediatric research has focused on the inventory of

pontaneously acquired postmorbid semantic knowledge, withhe exception of one study that investigated the ability to acquirenowledge de novo using an appropriate paradigm. In 2004, weublished the first prospective investigation of concepts acqui-ition in two children with profoundly impaired episodic mem-ry and low intelligence (Guillery-Girard, Martins, Parisot, &ustache, 2004). Our results revealed that they were able to

earn and maintain this information. Consequently, these resultsmphasized the findings of Vargha-Khadem and her collabora-ors (Baddeley et al., 2001; Gadian et al., 2000; Vargha-Khademt al., 1997) and supported the hierarchical conception of mem-ry developed by Tulving, which postulates that information can

each semantic memory quite independently of episodic mem-ry. Nevertheless, this study did not directly test the hypothesisdvanced by Squire and colleagues that residual episodic capac-ties are involved in semantic learning.

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794 S. Martins et al. / Neuropsy

The aim of the present research was to demonstrate semanticearning in childhood permanent amnesic syndrome, taking intoccount the actual involvement of residual episodic abilities inovel semantic acquisition. Accordingly, we conducted withinhe same design both the teaching of novel concepts and thessessment of phenomenological details that occurred during thecquisition of those concepts in order to identify the implicationf episodic residual abilities in new semantic acquisition. Ineeping with this idea, we proposed an original protocol to twomnesic children with different cerebral lesions and differenteuropsychological profiles.

. Method

The protocol, derived from our first prospective study (Guillery-Girard etl., 2004), consisted in the acquisition of eight new concepts (targets), eachomprising a label, a category and a set of features. It involved: (1) the semanticcquisition in the strictest sense, based on original material composed of picturesnd descriptive texts; (2) the assessment of the putative role of episodic memoryuring semantic acquisition by means of various tests. This protocol was dividednto five sessions. The first session consisted of both the assessment of semanticnowledge concerning familiar and targets items, and the first learning phasetself. The next three sessions were devoted to semantic learning and episodicssessments. The fifth session consisted in the postlearning assessment of targetss well as familiar items and episodic memories of the learning sessions.

.1. Semantic learning paradigm

The semantic learning design is detailed in Fig. 1. This semantic learningask featured eight new concepts. Each concept consisted of a label, its superor-

inate category and three specific features. The label was the only totally newnformation. Indeed, familiar categories and features were deliberately chosenn order to enhance their integration into the preexisting knowledge base. Thecquisition of each concept was supported by descriptive texts, one sentence perategory and feature, associated with one particular photo.

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ig. 1. Semantic learning paradigm. The specific design of the semantic learning taemantic knowledge of 8 familiar concepts and 8 new concepts (i.e., targets) by meaearning phases of the categories and features relative to these targets. (3) post-learnire-learning assessment.earning phases:Labels: During the first learning phase children were provided the photography ofthe “vanishing cues” method was applied, to facilitate the acquisition of the labels.derived technique based on the auditory-verbal modality was applied, using the samadded phonemes to the word, rather than letters.Categories and features: During the first phase, children began to learn the categoriesIn the second learning phase, after each description, they were asked an open-endephase, we applied the “errorless learning method”. However, despite repeated instexperimenter gave the correct answer. From the third learning phase onwards, onlypassive to an active state in the course of the semantic acquisition.

gia 44 (2006) 2792–2805

.1.1. Assessments of semantic knowledgeSeveral assessments of semantic knowledge were administered, one before

he learning phases (i.e., prelearning assessment) and one after learning (i.e.,ostlearning assessment), in order to test acquisition efficiency and stabilityver time. We also conducted additional post-learning assessments to test long-asting semantic maintenance. Every assessment included eight targets and eightdditional familiar concepts. All assessments comprised two distinct parts: (a)aming of photos of all the items; (b) a three-choice questionnaire relatingo each item. The first question was about the superordinate category and thehree others about different features. In the second postlearning assessmentcarried out 1 week later), we added the naming of the eight targets using pre-iously unseen photos to test the flexibility of the newly acquired conceptstargets).

.1.2. Learning phasesFour learning phases were administered after the prelearning assessment

or the teaching of the 8 targets. Each learning phase included two stages: (a)aming the targets and (b) learning the new concepts (category and features).rom the second learning phase we applied specific learning techniques. For the

earning of the targets’ labels, we applied both the vanishing-cues method andhe errorless-learning technique. For the acquisition of categories and featurese also used the errorless-learning method.

.2. Episodic memory assessments

The putative role of episodic memory in novel semantic acquisition wasnvestigated on several occasions using various recognition tasks (Fig. 2): (1)ecognition of contextual clues, which comprised the retrieval of general and

pecific contextual clues provided in one particular session. (2) Recognition ofargets, which was a yes/no recognition task of the photos used in the nam-ng task. This recognition task was associated with the Remember/Know (R/K)aradigm (Tulving, 1985). (3) Recognition of learning photos, which required

es/no recognition of photos used during the learning of concepts. Additionally,hildren were asked to justify their judgements by providing phenomenologi-al details. Some of these tasks, such as recognition of targets and recognitionf learning photos seen at many occasions might be partially realised withamiliarity-based retrieval. In contrast, the recognition of specific contextual

sk consisted of 3 stages: (1) a pre-learning assessment, i.e. an assessment ofns of a naming of the targets (i.e., label) and a 3 choice-questionnaire. (2) fourng assessments of semantic knowledge using the same questionnaire as in the

each target with the correct label. From the second learning phase onwards,When reading abilities were not sufficient, as in KF’s case and her controls, ae methodology as in the visual modality. Here, the experimenter removed or

and the features of the targets by watching photos and listening their description.d question about the feature that had been detailed. From the second learningructions, children produced several wrong answers. When this happened, theopen-ended questions were asked. Thus, the child deliberately moved from a

S. Martins et al. / Neuropsychologia 44 (2006) 2792–2805 2795

Fig. 2. Design of Episodic Memory Assessments. Several episodic assessments were carried out in sessions 2, 3 and 4, and during the post-learning sessions.Recognition of contextual clues: During the first 3 sessions, the experimenter introduced 8 specific events different in each session as (1) the room where the sessiontook place, (2) the clothes the experimenter worn, (3) the activity he proposed to the child, (4) the sweet he gave, (5) the sound the child heard, (6) the toy the childplaid with, (7) where a fragrance was diffused, and (8) the colour of the desk. Contextual clues provided in one session were tested in the following session using amultiple choice questionnaire.Recognition of the targets: In sessions 2 and 3, a yes/no recognition task was provided during the naming phase. The state of consciousness associated with therecognition of a photo was investigated by means of the Remember/Know paradigm. Then they named the corresponding target.Recognition of the learning photos: In post-learning sessions, children had to recognise learning photos of each target among related and non related lures. Thisrecognition task featured 4 types of photo: (1) photos used during semantic learning; (2) lures that were perceptually close to these; (3) previously unseen photos

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illustrating one feature described in the texts during session 1; (4) neutral photheir answer by the recollection of contextual details corresponding to one ophenomenological details related to the learning of the targets.

lues different from one session to another implies recollection-based retrievalnd thus utilise episodic processes as attested by the R/K paradigm.

.2.1. Recognition of contextual cluesIt was necessary to have objective and controlled clues to recollection from

ne session to the next. Consequently, we used different controlled contextual

lues in each session. These clues could be divided into two categories: sixeneral spatiotemporal clues and eight specific clues. The first clues were abouthen (season, day, etc.) and where (hospital, house, large or small office, etc.) therst three sessions took place. The second clues concerned events limited in time,hich occurred in one specific session only (clothes worn by the experimenter,

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ig. 3. Brain MRI of patient RH: (a) sagittal view (pre-surgery), MRI showed kyst ofvidenced damage to mammillary bodies.

hich differed from the acquired concepts. Additionally, children had to justifylearning sessions. For each item that was recognised, children had to provide

ecreation time of doing a puzzle, eating a sweet, etc.). These were introduced byhe experimenter at fixed times in sessions 1–3. The retrieval of clues provideduring a specific session was tested in the following session by means of aultiple-choice recognition task.

.2.2. Recognition of targets

In sessions 2 and 3, during the naming phase, children were first asked

o recognise the targets among lures. During this recognition task, the R/Karadigm was applied (Tulving, 1985). Children thus had to specify whether theylearly remembered (R) the phenomenological details of the learning episodevividness) or whether they just knew (K) they had encountered this picture

craniopharyngiom in the third ventricule; (b) sagittal view (post-surgery), MRI

2796 S. Martins et al. / Neuropsychologia 44 (2006) 2792–2805

Table 1Performances of RH, KF and her IQ-non-amnesic control (ConPatient) on neuropsychological tests

RH KF ConPatient

Intellectual efficiency WISC-IIIVerbal IQ 88 64 63Performance IQ 93 69 59Total IQ 89 62 52Comprehension 7 3 –Information 7 5 5Vocabulary 9 5 4

LanguageVerbal fluency >+ 1S.D. <1.5S.D. −1S.D.Repetition Normal Normal NormalNaming Normal <1.5S.D. NormalComprehension Normal Normal <1.5S.D.

Short-term memoryDigit span 4 3 4Visuo-spatial span 4 2 –

Long-term memorySemantic: knowledge scale of the K-ABC

Familiar people and places 76 59 74Arithmetic 88 64 68Riddles 57 72 –Read and decode 63 72 60Read and comprehension 84 – 70

EpisodicRivermead 13/22 4/20 16/22BEM: (Signoret’s memory efficiency battery)

Learning of 12 words 2–3 and 4/12 (z = −2.2) 1–3 and 3/12 (z = −2.3) 1–3 and 6 /12 (z = −1.5)Recall of 12 words 3/12 (z = −2.8) 0/12 (z = −3.7) 8/12 (z = −0.14)Immediate recall of a geometric figure – 1.5/12 (z = −3) –Delayed recall of a geometric figure 24/24 (z = +1) 1/12 (z = −3.1) –Recognition of 24 abstract figures – 11/24 (z = −1.6) 23/24 (z = +1.5)

Child memory scaleImmediate and delayed recognition of faces 11 and 8 4 and 5 –General index 62 – –Immediate and delayed verbal memory index 52 and 50 – –

Executive functionsTower of London

Number of success at the first trial 6/12 (z = −0.13) 5/12 (z = +0.42) –

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athological scores are mentioned in bold type.

efore but could not give any details of the context of the previous learninghase.

.2.3. Recognition of learning photosA final recognition task was administered at the end of the first (and second

dditional) postlearning assessments. Children had to recognise learning photosf each target among related and nonrelated lures. For each item that was recog-ised, children had to provide phenomenological details related to the learningf the targets.

.3. Patients

RH is a left-handed, 9.5-year-old boy. When he was 6 years old, he wasperated on for a craniopharyngioma complicated by a cyst on the third

entricle (December 2000). Fig. 3a and b shows MRI scans performed pre- andostoperatively. Both MRI showed a lesion focused on mammilary bodies bilat-rally. Two months later, he showed both retrograde (he could not remember hisriends) and anterograde amnesia. RH also suffered from severe spatiotemporalmpairment. When he was included in this study, RH’s overall cognitive abilities

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ere normal and homogeneous in the verbal and visuospatial fields (Table 1).e was thus able to follow the normal school curriculum, although he had beeneld back a year. Moreover, RH showed preserved working memory abilities.espite a significant improvement since his surgery, RH’s episodic memory

emained severely impaired. For example, when he was in the hospital, RHould not retrieve the way to return to the office, he asked iterative questionsespite repetitive answers (“What will we do?”; “At what time will the exercisetop?”; “Did we already meet?”). Several neuropsychological tests, such asearning a list of words (BEM, Jambaque, Dellatolas, Dulac, Ponsot, & Signoret,993) and delayed retrieval and ecological tests (Rivermead, RBMT, Wilson,vani-Chalian, Besag, & Bryant, 1993) revealed a pathological performance.evertheless, RH was able to perform visual recognition tests normally

RBMT). Recently, at 12 years of age, RH carried out another neuropsycho-ogical exam that showed lower memory performances using the adult versionf the RBMT (7/24). RH performed the whole protocol with two additional

ostlearning assessments, i.e., the prelearning assessment, four learning phasesnd three postlearning assessments (48 h, 1 week and 1 month of delay).

KF is a right-handed, 7-year-old girl. At 5 years of age, she suddenly exhib-ted status epilepticus 1 week after vaccination. The status epilepticus lasted0 days but the patient had no respiratory or cardiac failure. A brain MRI per-

S. Martins et al. / Neuropsycholo

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ig. 4. Brain MRI of patient KF: coronal view demonstrated atrophy in the leftnd right hippocampus.

ormed 1 week after the first seizure episode revealed hippocampal oedema; anRI performed 1 month later showed bi-hippocampal atrophy estimated at more

han 50% and disproportionate to the mild atrophy in the other areas (Fig. 4,ee Jambaque et al., 2006, for medical data and physiopathological discussion).ince this event, KF had suffered from bitemporal epilepsy and followed achool curriculum for special needs children. Moreover, she had behaviouralroblems, consisting mainly of a lack of inhibition, hyperactivity, offensiveanguage and inappropriate gestures. Nevertheless, this pathological behaviourad been decreasing over the previous few months. Neuropsychological assess-ents revealed severe anterograde amnesia with profound forgetfulness and

patiotemporal impairment (Table 1). Moreover she formulated numerous itera-ive questions and performed repetitive acts. Her overall cognitive abilities wereeficient, with heterogeneous performance. Nonetheless, KF had extensive lan-uage abilities and a normal level of comprehension, even though she presentedaming difficulties and impaired verbal fluency. During the neuropsychologicalssessments, KF was able to recognise a few letters (equivalent to first yearf primary school). Concerning executive abilities, KF was able to adapt hernswers to complex explanations; she could organize and plan sequences inrder to solve unusual situations (her performance was normal in the Tower ofondon test), but she remained impulsive and her performance was still labile

mainly due to frequent epileptic seizures). KF was particularly deficient inemory capacity. Indeed, she had poor working memory capabilities in both

erbal and spatial modalities. Above all, she suffered from major episodic mem-ry impairment, illustrated by profound and immediate forgetfulness. One yearater, we had the opportunity to conduct a new neuropsychological assessment.er behaviour had successfully changed in that she could control herself during

ll the testing, without any production out of purpose. This last neuropsycholog-cal assessment revealed that KF’s cognitive development was maturing. Indeed,he could conceptualize and elaborate responses far better than in the first assess-ent (WISC-III: similarities = 8; information = 5). Even though she succeeded

t that time in giving appropriate answers, these were incomplete and patho-ogical on the Vocabulary subtest (Vocabulary: 3). Her capacities in working

emory had increased slightly (digit span = 3, visual span = 3). By contrast, theace recognition test from the CMS confirmed her major episodic impairmentimmediate recognition: 4; delayed recognition: 2). KF performed more learn-ng sessions than RH due to both the severity of her amnesia and the multiplepileptic seizures. We also had the opportunity to test KF at differing delaysollowing the learning phase. Thus, she was provided a prelearning assessment,2 learning phases and 6 postlearning assessments (24 h, 48 h, 1 week, 1 month,months and 1 year of delay).

.4. Controls

To gain relevant evidence for episodic involvement in semantic acquisition,e conducted several comparisons between RH’s and KF’s performance and

hose of nonamnesic children.

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RH’s performance was compared with nine healthy children matched foroth age and IQ level (four boys and five girls; mean age = 9.1 years; S.D. = 2.1onths), following their fourth year of primary school. They all presented nor-al nonverbal intelligence (median = 0.62 in the Colour Progressive Matrice

PM47, Raven, 1998]). This control group, which is reported in tables and fig-res as “ConGroup,” participated in the five sessions (pre-/postlearning sessionsnd learning phases). One of these children, whose age was close to RH’s, car-ied out all the delayed postlearning assessments and is subsequently reporteds “ConSubject.” He was a right-handed, 9-year-5-month-old boy, with intactemory capacities, as confirmed by the BEM (scores between −0.6S.D. and1.2S.D. in both verbal and visual modalities).

Knowing that KF had low cognitive development combined with her amne-ia, we conducted the subsequent comparisons: Firstly, KF’s performance wasompared with nine healthy children (“ConGroup”) following their second yearf kindergarten, matched for developmental age (IQ) (six girls, three boys, meange = 5.2 years; S.D. = 3.8 months). Nonverbal intelligence of these nine chil-ren was above normal range (median = 0.83 in PM47). These children carriedut the prelearning assessment, the learning phases and two postlearning assess-ents (1 day and 1 week after the learning phase). Secondly, a healthy child,ho was matched for the level of schooling (she was following first grade),

arried out the entire protocol with the delayed assessments in order to com-are her performance with those of KF (“ConSubject”). This control was a-year-7-month girl, with normal episodic memory (17/18 in the Rivermeadehavioural memory test). Finally, to take into account the cognitive disabilitiesf KF, we compared her performance with those of one nonamnesic IQ-matchedirl (“ConPatient,” 8 years and 3 months old). Like KF, this girl followed a schoolurriculum for special needs children and suffered from epilepsy. When she was, she underwent several generalised epileptic seizures. She remained seizureree for this period, except for one recent epileptic episode in febrile context. Theeuropsychological assessment provided in 2005 revealed a limited cognitiveunctioning (Verbal IQ = 63; Performance IQ = 59; Global IQ = 52) and someifficulties in comprehension (Table 1). Nonetheless, her verbal capacities wereufficient to pursue the entire semantic paradigm. To ensure her episodic mem-ry preservation, we provided the same neuropsychological tests as KF. Thougher score on the RBMT seemed to be low, this nonamnesic IQ-matched girlerformed normally in all subtests, except for the appointment and the recallf history. In both these tasks, her failure was rather due to her inability tonderstand the instructions than to perform an episodic memory assessment.he preservation of episodic memory was confirmed by normal performance

n BEM.

.5. Statistical analyses

Various scores were recorded for each session: (1) concerning the seman-ic assessments, a naming score (max = 8), a flexibility score (consisting of theerformance in naming the targets through a new viewpoint, max = 8) and annswering score (max = 32); (2) concerning episodic memory, we recorded chil-ren’s responses in the several recognition tasks: recognition of contextual cluesmax = 14) carried out in sessions 2–4; recognition of targets (max = 8) associ-ted with R/K judgements during the naming tasks of session 2 and 3; recognitionf learning photos (correct recognition; false recognition; max = 8).

A linear regression analysis has been conducted for each target (the eighttems to acquire), and separately on label, category and features learning.

We compared amnesic children’s performance to their control group’s withscores analysis, with the corresponding cut-off (−1.86S.D.; p = .05, dl = 8 forH and −1.83S.D.; p = .05, dl = 9 for KF). We also calculated z scores for theonamnesic IQ-matched to KF (“ConPatient”).

. Results

.1. Semantic memory

.1.1. Naming task

.1.1.1. RH. Performance of RH and his controls (ConGroupnd ConSubject) for naming are reported in Table 2 for familiaroncepts and in Fig. 5a for target items.

2798 S. Martins et al. / Neuropsycholo

Table 2Performances of patients RH and KF compared with their controls (ConGroups,ConSubjects, ConPatient) in naming and questions concerning the familiar items

Pre-learning assessment Post-learning assessment

NamingRH 6 (z = −5.7**) 8 (z = +0.3)ConSubject 8 8ConGroup

Mean 7.9 7.9S.D. 0.3 0.3

KF 6 (z = −1.5) 8 (z = +0.4)ConPatient 5 (z = −2.8*) 6 (z = −1.5)ConSubject 8 8ConGroup

Mean 7.1 7.6S.D.

QuestionsRH 28 (z = −0.4) 28 (z = −0.9)ConSubject 32 32ConGroup

Mean 28.8 29.4S.D. 1.8 1.5

KF 20 (z = −1.6) 10 (z = −5.6**)ConPatient 16 (z = −2.9*) 18 (z = −2.9*)ConSubject 28 31ConGroup

Mean 25 25

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p ≤ 0.05; **p ≤ 0.0005. Pathological scores are mentioned in bold type.

3.1.1.1.1. Familiar items. RH performed significantlyorse than his control group in the prelearning session, whereasis score was identical to his controls in the postlearning sessionTable 2).

3.1.1.1.2. Target items. Though RH obtained pathologicalcores in the first postlearning session (z = −2.5), he globallyearned the labels as well as his control group (Fig. 5a). Indeed,is mean slope of learning did not statistically differ from Con-roup’s (z = −1.7). However, the per item analysis revealedifficulties in acquiring two of the eight labels (manatee: z = −3;hinese artichoke: z = −5.3).

In the 1-week-delayed postlearning semantic assessment,H’s naming score continued to increase, although his score

emained under his ConSubject (RH = 7/8; ConSubject = 8/8).he 1-month-delayed assessment showed a decrease in perfor-ance for both boys. However, RH was able to spontaneously

upply the first letter of the word (which he used as a clue) andas able to retrieve the labels if he were given the first phoneme.3.1.1.1.3. Flexibility. RH was able to give the targets’

roper labels when they were shown from a different viewpointflexibility score = 5/8 targets). In the same situation, his Con-ubject could name all the targets.

.1.1.2. KF. The performance of KF and her controls (Con-

roup, ConSubject, ConPatient) on naming familiar and targets

tems are reported in Table 2 and Fig. 6a, respectively.3.1.1.2.1. Familiar items. KF’s performance was in the

ormal range and above ConPatient’s scores in both the pre-nd postlearning assessment (Table 2).

n

3rt

gia 44 (2006) 2792–2805

3.1.1.2.2. Target items. Mean slopes of learning revealedhat KF performed similarly to both her ConGroup (z = −1.2)nd the ConPatient (Fig. 6a). Despite a slight decrease, hererformance in the postlearning assessments carried out afterntervals of 24 and 48 h revealed normal scores. This decreaseeemed to correlate with the onset of epileptic seizures a fewours before the assessment.

The per item analysis did not reveal any difficulty in acquiringne specific label.

Both assessments carried out after 1 month and 5 monthsevealed a decrease in her performances as well as those of heronSubject (the unique control who underwent the followingelayed sessions). However, KF was able to give the correctnswer for each target if the experimenter helped her by pro-ouncing the first phoneme. One year later, she was unableo name any of the targets, although she could correctly namehe familiar items. However, when the experimenter gave therst phonemes of the targets, KF gave labels that were phonet-

cally close to the real ones (e.g. “blenne” instead of “blennie,”dionie” instead of “dionee” and “tartie” instead of “tarsier”). Inhe same situation, her ConSubject could not name any of the tar-ets and was unable to retrieve this information using phoneticlues.

3.1.1.2.3. Flexibility. The 1-week-delayed naming taskevealed that KF was unable to give the labels when the targetsere presented from a different viewpoint (flexibility score = 1/8

argets). Nonetheless, given the individual variability in Con-roup (mean = 3.1; S.D. = 1.8), her performance was not statis-

ically pathological (z = −1.2).

.1.2. Acquisition of categories and features

.1.2.1. RH. The performance of RH and his control groupn questions about concepts (i.e., categories and features) areeported in Table 2 for the familiar items and in Fig. 5b for theargets.

3.1.2.1.1. Familiar items. RH performed exactly at theame range as controls for familiar items in pre- and postlearningssessments (Table 2).

3.1.2.1.2. Target items. RH showed a regular learningurve for the acquisition of the features. Even though hiscores remained under the ConGroup in the first postlearningssessment (z = −3.5), the learning mean slope revealed thatH acquired the novel information as well as his ConGroup

z = +1.9) (Fig. 5b).Regarding the per item analysis, it appeared that RH learned

he eight concepts at the same rate as the ConGroup. Analy-is focusing on categories and features separately confirmedormal learning, except for two features (one referring to theanatee: z = −2.7; the other referring to the medlar: z = −2.3)

Fig. 5b).The assessments conducted 1 week and 1 month later revealed

hat RH’s results decreased slightly for this period, whereas thisovel knowledge was comparable to the ConSubject.

.1.2.2. KF. The KF performance and controls on questions areeported in Table 2 and Fig. 6b for the familiar items and theargets respectively.

S. Martins et al. / Neuropsychologia 44 (2006) 2792–2805 2799

d with

aw

ttCflsm

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otmb

seosfirgs

Fig. 5. Performance of patient RH compare

3.1.2.2.1. Familiar items. KF performed at the same ranges her ConGroup in the prelearning session but significantlyorse in the first postlearning assessment (Table 2).3.1.2.2.2. Target items. It took KF 12 sessions to acquire

he eight concepts, and her performance remained under bothhe ConGroup’s (z = −5.7 in the 12th learning session) and heronSubject (Fig. 6b). It is noteworthy that KF’s performanceuctuated with her epileptic seizures. Notably, she had sufferedix epileptic seizures the night before the 24 h delayed assess-ent and thus was in a state of irritability.The per item analysis showed that KF’s performances were

ower than her ConGroup’s for all the targets except for the pan-olin. Focusing on the acquisition of the categories, it appearedhat KF learned each category normally, except for the pangolin

which was taught to not pertain to any species; z = −5.7). Oth-rwise, KF’s performances were statistically different from herontrols in all the features. Conversely, ConPatient acquired nor-ally all the categories and the features.

oadA

his controls (ConSubject and ConGroup).

In the delayed sessions, KF’s results improved after intervalsf 48 h and 1 week, even though her performance remained underhose of her controls (z = −4 in the second postlearning assess-

ent). Postlearning assessments revealed a marked decrease foroth ConSubject and KF between 1- and 5-month delays (Fig. 6).

One year later, KF underwent a further semantic assessment,pecially designed to assess the stability of the semantic knowl-dge she had learned. Initially, she carried out a recognition taskf the eight targets hidden among eight equivalent new conceptshe had never seen before (e.g. the “aye-aye”). She recognizedve of the eight previously acquired concepts and made no falseecognition. Her control SJ succeeded in recognizing every tar-et. Moreover, KF had no significant memory of where and whenhe had learned these concepts and, after much prompting, was

nly able to say that she might have acquired this informationt the hospital. However, her control gave phenomenologicaletails of the encoding episodes (see episodic memory section).fter the naming task, KF answered the same questionnaire as

2800 S. Martins et al. / Neuropsychologia 44 (2006) 2792–2805

F nPatit ed byb

ifS

swRr

3

T

3

p

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3

ig. 6. Performance of patient KF compared with her controls (ConSubject, Cohe depth of her amnesia and her epileptic attacks. (!) KF’s sessions were precedy fluctuations in performance both for targets and known items).

n the other semantic assessments and obtained 10/32 for theamiliar concepts and 16/32 for the targets. Thus, like her Con-ubject, she performed better than she had 1 year earlier.

It is noteworthy that amnesic children and the ConPatient hadome difficulties in respecting errorless learning instructions,hereas their healthy controls did well. Several examples fromH, KF and ConPatient’s productions and percentage of false

esponses are reported in Appendix A.

.2. Episodic memory

Data concerning recognition tasks are provided inables 3 and 4.

.2.1. Recognition of contextual clues

Data concerning the recognition of the contextual clues are

rovided in Table 3.On the contextual clue recognition tasks carried out in ses-

ions 2–4, RH was significantly impaired compared to his Con-

r(pt

ent, ConGroup). *Learning phases: KF was given several extra sessions due toseveral epileptic attacks during the night (NB: epileptic attacks were followed

roup. When focusing on each kind of contextual clues, itppeared that his performance was worse for retrieving generallues than specific clues in session 2, equally impaired in ses-ion 3 and less impaired in general clues than specific contextuallues in session 4.

On this task, KF was significantly impaired when comparedo the controls. Indeed, her total score was pathological forach session. Regarding general versus specific contextual clues,esults revealed that KF was more impaired in retrieving specifichan general clues. Conversely, ConPatient performed normallyn all these recognition tasks.

.2.2. Recognition of targetsData concerning targets recognition are reported in Table 4.Like his controls, RH recognized the targets without any false

ecognition. RH gave more Remember (R) responses than KnowK) responses in session 2 than his ConGroup. However, thisattern reversed in session 3, RH giving significantly fewer Rhan K responses, contrary to the ConGroup.

S.Martins

etal./Neuropsychologia

44(2006)

2792–28052801

Table 3Performances of RH and KF with their respective controls (ConSubjects and ConGroups, ConPatient) on the recognition of contextual clues

Recognition of contextual clues

Session 2 Session 3 Session 4

General clues (/6) Specific clues (/8) Total (/14) General clues (/6) Specific clues (/8) Total (/14) General clues (/6) Specific clues (/8) Total (/14)

RH 5 (z = −2.6*) 7 (z = −0.9) 12 (z = −1.9*) 5 (z = −2.6*) 7 (z = −2.6*) 12 (z = −3.3**) 5 (z = −1.9*) 4 (z = −7.1***) 9 (z = −6.7***)ConSubject 6 7 13 6 8 14 6 8 14

ConGroupMean 5.8 7.4 13.3 5.8 7.8 13.6 6.1 7.6 13.7S.D. 0.3 0.5 0.7 0.3 0.3 0.5 0 0.5 0.5

KF 3 (z = −2.2*) 2 (z = −5.8***) 5 (z = −5.8***) 1 (z = −3.5**) 2 (z = −6.6***) 3 (z = −5.58***) 3 (z = −2.3*) 1 (z = −8.9***) 4 (z = −5.3***)ConPatient 5 (z = −0.3) 8 (z = 1) 13 (z = 0.5) 5 (z = 0.1) 7 (z = −0.2) 12 (z = −0.1) 5 (z = −0.3) 8 (z = 0.9) 13 (z = 0.5)ConSubject 6 8 14 5 7 12 3 8 14

ConGroupMean 5.3 7.1 12.4 4.9 7.2 12.1 5.3 7.3 12.2S.D. 1.1 0.9 1.3 1.1 0.8 1.6 1 0.7 1.6

*p ≤ 0.05; **p ≤ 0.005; ***p ≤ 0.0005. Pathological scores are mentioned in bold type.

Table 4Performances of RH compared with their respective controls (ConSubject and ConGroup) on targets recognition

Targets recognition

Session 2 Session 3

Hit recognitions (8) False recognitions (4) Remember Know Hit recognitions (8) False recognition (4) Remember Know

RH 8 (z = +0.3) 0 (z = 0) 5 (z = −1.4) 3 (z = 1.7) 8 (z = +0.3) 0 (z = 0) 1 (z = −4.1*) 7 (z = +4.1*)ConSubject 8 0 8 0 8 0 7 1

ConGroupMean 7.9 0 7 0.8 8 0 6 1.3S.D. 0.3 0 1.4 1.2 0 0 1.3 1.4

KF performances are not reported in the table since R/K responses have not been analysed. However, she and her ConPatient obtained 8/8 in recognition during both sessions and with no false recognition.*p ≤ .005. Pathological scores are mentioned in bold type.

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802 S. Martins et al. / Neuropsy

KF and all her controls recognized all the targets without anyalse recognition. We preferred not report R/K results since thisrocedure is difficult to apply in children younger than 6 yearsld (Brainerd, Holliday, & Reyna, 2004), and most controls werenable to understand the specific instructions.

.2.3. Recognition of learning photosRH and his controls showed similar performance (8/8 for

H and mean ConGroup = 7.7; S.D. = 0.5). All the photos usedn the learning phase were correctly recognized (with any falseecognition neither in the first postlearning assessment nor in theecond one). Nevertheless, RH justified his answers by givingrroneous details (“I’ve only seen it once and that was at home”),hereas the ConGroup and ConSubject gave explanations basedn accurate spatiotemporal clues (“I saw it Thursday and Fri-ay with you”). When asked for phenomenological details, RHould only retrieve that he ate a sweet but could not recall wherend when. Conversely, his controls were able to recall manyhenomenological details referring to places and times but alsopecific events (“We played with the Memory Game, we laughed,t was 2 days ago . . .”).

KF obtained similar performance (7/8) to her controlsmean = 8) in the first and second postlearning sessions withoutaking any false recognition, while her ConGroup and Con-ubject provided false recognitions (first postlearning session:ean ConGroup = 0.3; S.D. = 0.5; ConSubject = 1; second learn-

ng session: mean ConGroup = 1.6; S.D. = 1.7; ConSubject = 5).hese false recognitions of the ConGroup concerned the lures

elating to the properties that had been verbally described. WhenF was asked to retrieve phenomenological details, she justifieder recognition judgements by providing semantic informationfor “blenny”: “it walks on the bottom of the sea, it’s a fish,”it eats bees”). This was also observed in controls. However,hen the experimenter asked for events that occurred during the

earning sessions, KF could not answer, whereas her controlsave more details about the learning context (“I remember thatt was during the exercises for the Chinese artichoke. I was withou, and we made a puzzle.”).

One year later, KF failed to retrieve events that had occurreduring the experiment and did not recognise either the depart-ent of neurology or the physician, unlike her control who

ucceeded in recalling phenomenological details.

. Discussion

This prospective research provides new evidence for de novocquisition of multicomponent concepts in childhood amnesicyndrome, while it strengthens the idea that this learning canccur without episodic memory involvement.

Firstly, patients were able to learn the labels at the same rate asheir respective controls contrasting with our initial exploratorytudy (Guillery-Girard et al., 2004). Thus, the vanishing cuesethod as applied in this work seems particularly effective in

acilitating the acquisition of new labels in childhood (GliskyDelanay, 1996; Hunkin & Parkin, 1995), even in children

ith reading disabilities since KF reached a good level in nam-ng tasks with the auditivoverbal version. Although the stability

eeRl

gia 44 (2006) 2792–2805

f these acquisitions varied between children, they were allble to retrieve labels after several delays when provided withhonological clues. However, both healthy and amnesic chil-ren experience difficulties in naming targets with new photos,hich prevent us from determining whether this new acquisi-

ion is flexible or not. Their difficulties might result from eitherubtle visuospatial dysfunctions (Lee et al., 2005; Pihlajamakit al., 2004) preventing them from manipulating new represen-ations normally and/or from the learning techniques appliedn this protocol themselves. Several studies have indeed high-ighted a narrowness of novel abilities acquired this way (Glisky,chacter, & Tulving, 1986b; McKenna & Gerhand, 2002; Vaner Linden et al., 1994). To minimise this hyperspecific learning,t would thus be interesting to provide more learning sessions forhe same concepts, showing them from different viewpoints. (seetark, Stark, & Gordon, 2005 for methodological outcomes).

Secondly, concerning the acquisition of categories, RH andF demonstrated normal learning for all the targets, apart fromF who failed in learning the category of the pangolin. Inter-

stingly, the pangolin was taught as “an animal so bizarre thatt does not pertain to any species.” Knowing that new informa-ion had to be anchored to preexisting semantic network to becquired (Stokto et al., 2004), atypical information, such as theangolin, might necessitate a good level of conceptualisation toe integrated, which KF lacks. Thus, previous failures to demon-trate amnesic patients’ learning of categories might be due todditional conceptualisation disabilities (Kitchener & Squire,000) but these were rarely reported in amnesia literature.

Focusing on the acquisition of features, we strongly con-rmed that amnesic children can learn new semantic infor-ation (Guillery-Girard et al., 2004; Vargha-Khadem et al.,

997). Furthermore, we report for the first time the stabilityf newly acquired semantic information in childhood amnesia,otably in a young girl who suffered from bilateral hippocam-al damage and who underwent intractable mesiotemporal lobeeizures. These data contrast with theories of consolidation pos-ulating that “seizures might disrupt the medial temporal lobe-eocortical interaction that may be essential for storing links inhe medial temporal lobes with increasing redundancy” (Blake,

roe, Breen, & McCarthy, 2000; Mayes et al., 2003, p. 600;cCarthy, Kopelman, & Warrington, 2004; Kapur et al., 1997).

o gain relevant evidence for the impact of epileptic seizuresn consolidation processes, it would be informative to carryut the same protocol in epileptic children with various tem-oral lobe seizure frequencies (for severe amnesia in epilepsy,ee Guerreiro, Jones-Gotman, Andermann, Bastos, & Cendes,001).

One may wonder why RH learned normally, while KF’scquisition remained lower and slower than her controls’. RH’sRI revealed that the lesions were focused on mammillary bod-

es, whereas the entorhinal and perirhinal cortex were sparednd the hippocampi preserved. By contrast, KF’s MRI showedajor hippocampal atrophy bilaterally and suggest that the

ntorhinal and perirhinal cortex partially suffered from the statuspilepticus. That is, we can hypothesise that difference betweenH’s and KF’s semantic profiles may rely on the extent of

esions in the mesial temporal lobes as even discussed in adults

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S. Martins et al. / Neuropsy

Verfaellie, Koseff, & Alexander, 2000). However, in our report,oth children acquired new semantic information, which sug-ests peculiarity in semantic acquisition in childhood amnesiaompared with adulthood amnesia. “Without well-functioningippocampal system, acquisition of semantic memory is slownd effortful, at least in adulthood. It is possible, however,hat in childhood, structures mediating semantic memory (. . .)an form new representations easily without benefit of the hip-ocampus.” (p. 42, Moscovitch et al., 2005). Vargha-Khademt al. (1997) reported normal or near normal knowledge, spon-aneously acquired, through uncontrolled repeated exposures,n patients who reached adolescence. Thus, KF’s relative slow-ess to acquire during our prospective protocol might mostlyesult from little repetitions. Furthermore, despite “errorlessearning” instructions, KF showed great difficulty in inhibitingnappropriate answers, iterative questions, a previous answer,r an impulsive answer to open-ended questions (she providedgrass” on several session when she was asked for the food ofhe pangolin). Her systematic mistakes may have reinforced thencoding of irrelevant answers because of their perseverativeature (Tulving, 1993). Similarly, her nonamnesic IQ controlConPatient) provided wrong answers, her performance remain-ng under controls (even if the difference is not statisticallyignificant). Taken together these data strengthen the involve-ent of executive functions in learning new facts, suggesting

hat the semantic impairment reported in previous retrospec-ive studies (Levin et al., 1996; Ostergaard, 1987; Broman etl., 1997) may arise partly from deficits in executive functionsindering the spontaneous acquisition of academic knowledge,ather than from semantic impairment per se.

However these assumptions did not strongly bring evidenceor or against the putative role of residual episodic abilities inew semantic acquisitions. To solve this issue, it was of majornterest to investigate the residual episodic abilities of eachmnesic child. Our recognition tasks therefore differed in regardith possible implication of episodic and/or semantic memories

espectively. Thus, recognition of targets, recognition of learn-ng photos seen at many occasions and general contextual cluesecognition might be partially realised on the basis of a feel-ng of familiarity. In contrast, recognition of specific contextuallues might imply recollection-based retrieval and thus utilisepisodic processes.

Firstly, we demonstrated that both RH and KF were ableo recognise learning photos normally, but neither could recallhenomenological details relative to the learning sessionsn which they repeatedly encountered the photos. Secondly,hey were strongly impaired in recognition of the contextuallues with remarkable difference between retrieval of generalersus specific clues, which demonstrate a dissociation betweenamiliarity and recollection-based processes. However, RH andF did not show the same pattern of results, RH being able to

ecognize several specific clues, may be due to, the extent andocation of his lesions partially sparing hippocampal structures

nd thus episodic memory. That is, RH might have answeredy recollecting some clues, what could explain above chanceerformance, whereas KF might have answered only throughfeeling of familiarity (supported by perirhinal cortex). This

gia 44 (2006) 2792–2805 2803

ssumption is supported by the R/K paradigm. Indeed, RH’sudgements were identical to controls in session 2 but reverse inession 3. This peculiar pattern of performance may result fromn increased delay between sessions 1 and 2 (4 h) to sessions 2nd 3 (20 h).

In summary, we show that amnesic children are capable ofew semantic acquisition comprising labels, categories and fea-ures. For the first time we demonstrate that, despite diencephalicr mediotemporal lobe injuries (including the hippocampus andurrounding structures), amnesic children showed long-termetention of newly acquired information. Nonetheless, the loca-ion and the extent of lesions might account for learning slownessince diencephalic impairment allows normal learning speed,hile hippocampal damage prevents normal acquisition. Thus,ippocampal structures might play a role in easy learning byupporting episodic efficiency, even though its impairment doesot prevent semantic acquisition. This study therefore supportsulving’s theory that the semantic acquisition of novel informa-

ion does not necessarily require episodic memory. Furthermore,ur observations corroborate those reported by Vargha-Khademnd her colleagues (Baddeley et al., 2001; Gadian et al., 2000;argha-Khadem et al., 1997) and take these authors’ conclusionne step further, as KF and RH took part in our prospective studyuring early childhood and only 2 or 3 years after their disease.

Above and beyond theoretical issues, this study demonstrateshe efficiency of several techniques in enhancing children’s gen-ral knowledge (Rankin & Hood, 2005; Wright & Limond,004). As such, it argues the case for memory rehabilitationn early childhood using the original methodology applied here,ven children with general cognitive disabilities.

cknowledgements

We wish to thank Suzanne Aschoff for reviewing the Englishtyle. Prof. Carel, Dr. Peudonier and Dr. Chiron for referring usH, KF and the nonamnesic IQ control, and Prof. Aubourg andr. Hertz-Pannier for the children’s MRI scans. We thank also

ll the controls and their families who agreed to carry out ouraradigm.

ppendix A. Examples of responses formulated by RH,F and ConPatient in various sessions, despite the

rrorless-learning instructions

tems questions (andanswer)

RH KF ConPatient

hinese artichokesWhat are the Chinese

artichokes?(vegetable)

We throw theChristmas-treeaway

A shellfish

In the morning

When could we eat it?(Christmas)

During thewinter

What does it look like?(chenille)

A shell

2 cholo

B

P

T

R

B

B

B

B

B

B

G

G

G

G

G

G

G

H

J

J

K

K

L

L

M

M

M

M

M

M

O

O

P

R

R

R

S

S

S

S

T

T

T

804 S. Martins et al. / Neuropsy

lennyWhat family the blenny

belong to? (fish)Blenny

Where does it live?(marsh)

In the water In the waterIn algae In the sea

uffinWhere does it live?

(Atlantic islands)In the ocean In the oceanOn the beach On the rocksIn the water

Where does it make itsnest? (in a burrow)

On the trees In nests

otal of bad responsesrecorded acrosslearning sessions (%)

8% 52% 20%

eferences

addeley, A., Vargha-Khadem, F., & Mishkin, M. (2001). Preserved recog-nition in a case of developmental amnesia: Implications for the acquisi-tion of semantic memory. Journal of Cognitive Neuroscience, 13, 357–369.

ayley, P. J., & Squire, L. R. (2004). Failure to acquire new semantic knowledgein patients with large medial temporal lobe lesions. Hippocampus, 2.

lake, R. V., Wroe, S. J., Breen, E. K., & McCarthy, R. A. (2000). Acceleratedforgetting in patients with epilepsy: Evidence for an impairment in memoryconsolidation. Brain, 123, 472–483.

rainerd, C. J., Holliday, R. E., & Reyna, V. F. (2004). Behavioral measure-ment of remembering phenomenologies: So simple a child can do it. ChildDevelopment, 75, 505–522.

rizzolara, D., Casalini, C., Montanaro, D., & Posteraro, F. (2003). A case ofamnesia at an early age. Cortex, 39, 605–625.

roman, M., Rose, A. R., Hotson, G., & MacCarthy-Casey, C. (1997).Severe anterograde amnesia with onset in childhood as a result of anoxicencephalopathy. Brain, 120, 417–433.

abrieli, J. D. E., Cohen, N. J., & Corkin, S. (1988). The impaired learningof semantic knowledge following bilateral medial temporal lobe resection.Brain and Cognition, 7, 157–177.

adian, D. G., Aicardi, J., Watkins, K. E., Porter, D. A., Mishkin, M., & Vargha-Khadem, F. (2000). Developmental amnesia associated with early hypoxic-ischemic injury. Brain, 123, 499–507.

lisky, E. L., Schacter, D. L., & Tulving, E. (1986). Learning and retentionof computer-related vocabulary in memory-impaired patients: Method ofvanishing cues. Journal of Clinical and experimental Neuropsychology, 8,292–312.

lisky, E. L., & Delanay, S. M. (1996). Implicit memory and new semanticlearning in post-traumatic amnesia. Neuropsychological Rehabilitation, 5,299–318.

uerreiro, C. A. M., Jones-Gotman, M., Andermann, F., Bastos, A., & Cen-des, F. (2001). Severe amnesia in epilepsy: Causes, anatomopsychologicalconsiderations, and treatment. Epilepsy & Behavior, 2, 224–246.

uillery, B., Desgranges, B., Katis, S., De la Sayette, V., Viader, F., & Eustache,F. (2001). Semantic acquisition without memories: Evidence from transientglobal amnesia. NeuroReport, 12, 1–5.

uillery-Girard, B., Martins, S., Parisot, D., & Eustache, F. (2004). Semanticacquisition in childhood amnesic syndrome: A prospective study. NeuroRe-port, 15, 377–381.

unkin, N. M., & Parkin, A. J. (1995). The method of vanishing cues: Anevaluation of its effectiveness in teaching memory-impaired individuals.Neuropsychologia, 33, 1255–1279.

ambaque, I., Dellatolas, G., Dulac, O., Ponsot, G., & Signoret, I. J. (1993).Verbal and visual memory impairment in children with epilepsy. Neuropsy-chologia, 31, 1321–1337.

ambaque, I., Hertz-Pannier, L., Mikaeloff, Y., Martins, S., Peudonier, S., Dulac,O., & Chiron, C. (2006). Severe memory impairment in a child with bihip-

T

T

gia 44 (2006) 2792–2805

pocampal injury after status epilepticus. Developmental Medicine and ChidNeurology, 48, 223–226.

apur, N., Millar, J., Colbourn, C., Abbott, P., Kennedy, P., & Docherty, T.(1997). Very long-term amnesia in association with temporal lobe epilepsy:Evidence for multiple-stage consolidation processes. Brain and Cognition,35, 58–70.

itchener, E. G., & Squire, L. R. (2000). Impaired verbal category learning inamnesia. Behavioral Neuroscience, 114, 907–911.

ee, A. C. H., Bussey, T. M., Murray, E. A., Saksida, L. M., Epstein, R. A.,Kapur, N., et al. (2005). Perceptual deficits in amnesia: Challenging themedial temporal lobe ‘mnemonic’ view. Neuropsychologia, 43, 1–11.

evin, H. S., Fletcher, J. M., Kusnerik, L., Kufera, J. A., Lilly, M. A., Duffy, F.F., et al. (1996). Semantic memory following paediatric head injury: Rela-tionship to age, severity of injury, and MRI. Cortex, 32, 461–478.

anns, J. R., Hopkins, R. O., & Squire, L. R. (2003). Semantic memory and thehuman hippocampus. Neuron, 38, 127–133.

ayes, A. R., Isaac, C. L., Holdstock, J. S., Cariga, P., Gummer, A., & Roberts,N. (2003). Long-term amnesia: A review and detailed illustrative case study.Cortex, 39, 567–603.

cCarthy, R. A., Kopelman, M. D., & Warrington, E. K. (2004). Remember-ing and forgetting of semantic knowledge in amnesia: A 16-year follow-upinvestigation of RFR. Neuropsychologia, 43, 356–372.

cKenna, P., & Gerhand, S. (2002). Preserved semantic learning in an amnesicpatient. Cortex, 38, 37–58.

ilner, B. (1959). The memory defect in bilateral hippocampal lesions. Psychi-atric Research Report of American Psychiatric Association, 11, 43–52.

oscovitch, M., Rosenbaum, R. S., Gilboa, A., Addis, D. R, Westmacott, R.,Grady, C., et al. (2005). Functional neuroanatomy of remote episodic, seman-tic and spatial memory: A unified account based on multiple trace theory.Journal of Anatomy, 207, 35–66.

’Kane, G., Kensinger, E. A., & Corkin, S. (2004). Evidence for semantic learn-ing in profound amnesia: An investigation with Patient H.M. Hippocampus,14, 417–425.

stergaard, A. L. (1987). Episodic, semantic and procedural memory in a caseof amnesia at an early age. Neuropsychologia, 25, 341–357.

ihlajamaki, M., Tanila, H., Kononen, M., Hanninen, T., Hamalainen, A., Soini-nen, H., et al. (2004). Visual presentation of novel objects and new spatialarrangements of objects differentially activates the medial temporal lobesubareas in humans. European Journal of Neuroscience, 19, 1939–1949.

ankin, P. M., & Hood, J. (2005). Designing clinical interventions for childrenwith specific memory disorders. Pediatric Rehabilitation, 8, 283–297.

aven, J. C. (1998). Progressives Matrices Couleur. Paris: Editions et Applica-tions Psychologiques.

osenbaum, R. S., Kohleer, S., Schacter, D. L., Moscovitch, M., Westmacott,R., Black, S. E., et al. (2005). The case of K.C.: Contributions of a memory-impaired person to memory theory. Neuropsychologia, 43, 989–1021.

quire, L. R. (1992). Memory and the hippocampus: A synthesis from findingswith rats, monkeys and humans. Psychological Review, 99, 195–231.

quire, L. R., & Zola, S. M. (1998). Episodic memory, semantic memory, andamnesia. Hippocampus, 8, 105–211.

tark, C., Stark, S., & Gordon, B. (2005). New semantic learning and general-ization in a patient with amnesia. Neuropsychology, 19, 139–151.

tokto, B. G., Kensiger, E. A., Locascio, J. J., Einstein, G., Rubin, D. C., Tupler,L. A., et al. (2004). Puzzling thoughts for HM: Can new semantic informationbe anchored to old semantic memories? Neuropsychology, 18, 756–769.

ulving, E. (1985). How many systems are there? American Psychologist, 40,385–398.

ulving, E. (1993). Self-knowledge of an amnesic individual is representedabstractly. In T. K. Sdrull & R. S. Wyer Jr. (Eds.), The mental representa-tion of trait and autobiographical knowledge about the self (pp. 147–156).Hillsdale, NJ: Lawrence Erlbaum Associates.

ulving, E. (1995). Organization of memory: quo vadis? In M. S. Gazzaniga(Ed.), The cognitive neurosciences (pp. 839–847). Cambridge, Mass: The

MIT Press.

ulving, E. (2001). Episodic memory and common sense: How far apart? Philo-sophical Transactions of the Royal Society of London (B), 356, 1505–1515.

ulving, E. (2002). Episodic memory: From mind to brain. Annual Review ofPsychology, 53, 1–125.

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V

V

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W

S. Martins et al. / Neuropsy

ulving, E., Hayman, C. A. G., & Macdonald, C. A. (1991). Long lastingperceptual priming and semantic learning in amnesia: A case experiment.Journal of Experimental Psychology: Learning, Memory, and Recognition,17, 595–617.

ulving, E., & Markowitsh, H. (1998). Episodic and declarative memory: Roleof the hippocampus. Hippocampus, 8, 198–204.

an der Linden, M., Cornil, V., Meulemans, T., Ivanoiu, A., Salmon, E., &Coyette, F. (2001). Acquisition of a novel vocabulary in an amnesic patient.

Neurocase, 7, 283–293.

an der Linden, M., Meulemans, T., & Lorrain, D. (1994). Acquisition of newconcepts by two amnesic patients. Cortex, 30, 305–317.

argha-Khadem, F., Gadian, D. G., Watkins, K. E., Connelly, A., Van Paess-chen, W., & Mishkin, M. (1997). Differential effects of early hippocam-

W

W

gia 44 (2006) 2792–2805 2805

pal pathology on episodic and semantic memory. Science, 277, 376–380.

erfaellie, M., Koseff, P., & Alexander, M. P. (2000). Acquisition of novelsemantic information in amnesia: Effects of lesion location. Neuropsycholo-gia, 38, 484–492.

estmacott, R., & Moscovitch, M. (2001). Names and words without meaning:Incidental postmorbid semantic learning in a person with extensive bilateralmedial temporal damage. Neuropsychology, 15, 586–596.

ilson, B. A., Ivani-Chalian, R., Besag, F. M. C., & Bryant, T. (1993). Adaptingthe rivermead behavioural memory test for use with children aged 5–10years. Journal of Clinical and Experimental Neuropsychology, 15, 474–486.

right, I., & Limond, J. (2004). A developmental framework for memory reha-bilitation in children. Pediatric Rehabilitation, 7, 85–96.