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Handbook of Clinical Neurology, Vol. 111 (3rd series) Pediatric Neurology Part I O. Dulac, M. Lassonde and H.B. Sarnat, Editors © 2013 Elsevier B.V. All rights reserved

c0135 Chapter 27 disorders in children

STEVE MAJERUS1, 2* AND MARTIAL VAN DER LINDEN1, 3 1Department of Psychology — Cognition & Behavior, University of Lige, Lige, Belgium 2Fonds de la Recherche Scientifique — FNRS, Brussels, Belgium 3University of Geneva, Geneva, Switzerland

s0005 THE DIFFERENT MEMORY SYSTEMS short-term memory, visuospatial representations for p0005 Memory impairments are observed in a broad range of visuospatial short-term memory) (Majerus et al., 2010). childhood disorders, either related to direct brain insult A further function of short-term memory is to mani- (, cerebrovascular accident) or to pulate and transform currently maintained information genetic anomalies leading to alterations of brain develop- (i.e., ) and as such is also strongly ment. Although different theoretical frameworks of related to executive functions and . memory functions currently coexist, there is agreement A second system is episodic long-term memory allow- p0015 on the existence of at least four different memory sys- ing the , , and retrieval of information as- tems. Rarely a child will present impairment in all of these sociated with the precise spatiotemporal context in which systems at the same time. Hence, for efficient diagnosis the information was experienced (e.g., remembering and treatment, the identification of impaired as well as one’s last birthday party, remembering the day when preserved memory functions is of utmost importance. one was awarded his/her high school diploma, remember- p0010 A first memory function is short-term memory ing the holidays spent in Norway last year, remembering (working memory, immediate memory, primary mem- the phone call received 10 minutes ago). As such, episodic ory) which holds currently perceived or retrieved infor- memory is intimately related to mation in an active and conscious format during the and the construction of one’s identity as an individual with completion of a cognitive task (e.g., maintaining an un- a history of personal events. also has a familiar telephone number one has just looked up in the future-oriented function by enabling us to think of future phone book, for the time needed to dial the number; events (the tasks-to-do today, tomorrow; medical and pro- maintaining a new melody or a new word one has just fessional appointments; planned meetings with friends). heard for immediate repetition; maintaining the succes- Another long-term memory system is semantic mem- p0020 sive results of an arithmetic problem during mental cal- ory storing general knowledge, scripts, and facts about culation; maintaining the picture of an unfamiliar object the world (e.g., What is a dog? What is a house? What do one is copying). Short-term memory allows us to inte- we do at a restaurant? Which is the capital of Belgium? grate current information with the immediate past and Why is it cold during winter?). Contrary to episodic long- the immediate future and hence is a critical function term memory, no precise contextual information is asso- for maintaining internal thoughts and activated cogni- ciated with semantic : we simply know that tive representations synchronized with ongoing external Brussels is the capital of Belgium, even if we do not events. Traditionally, verbal and visuospatial short-term know where and when we learned this information. Re- memory subsystems are distinguished although current trieval in is usually fast and easy, research suggests that both systems rely on common at- while it is slower and effortful in episodic memory. Se- tentional processes which interact with distinct represen- mantic memory is also a contributor to autobiographical tational bases (language representations for , by storing self-relevant but decontextualized

*Correspondence to: Dr. Steve Majerus, Department of Psychology – Cognition & Behavior, Universite´ de Lie`ge, Boulevard du Rectorat, B33, 4000 Lie`ge, Belgium. Tel: þ32 4 3664656, E-mail: [email protected]

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2 S. MAJERUS AND M. VAN DER LINDEN knowledge such as the date one was born, one’s nation- Three cases have been described presenting a selective ality, the names of close relatives. Semantic memories verbal short-term memory disorder in the absence of are often acquired implicitly, but they can be retrieved any documented brain insult, but with the predicted ac- explicitly while episodic memories are acquired and re- companying difficulties in learning new verbal informa- trieved explicitly. tion (Baddeley, 1993; Baddeley and Wilson, 1993; Hanten p0025 Finally, procedural long-term memory is a relatively and Martin, 2001). However, at least for two of these heterogeneous concept broadly regrouping complex cases, more general language impairment could not be sensorimotor knowledge and skills that are acquired completely excluded. implicitly or explicitly and, once fully automatized, are At the same time, short-term memory disorders are p0040 difficult to verbalize (e.g., skilled reading, speaking, most often observed in association with broader cogni- writing, advanced music playing, running a cycle, skilled tive impairment. Children with specific language im- typing on a computer keyboard). pairment and children with dyslexia typically show poor verbal short-term memory and working memory spans; the reduction in verbal short-term memory in s0010 SHORT-TERM MEMORY DISORDERS these populations cannot be fully explained by their p0030 Impaired short-term memory is reflected by a reduced poor language abilities, and hence it is likely that ability to temporarily store and reproduce verbal and/or the short-term memory deficits further contribute to visuospatial information that has just been presented. the already protracted language development in these Children with impaired verbal short-term memory will children. More generally, verbal short-term memory thus show poor ability in the immediate reproduction of deficits are a residual deficit in many populations which verbal sequences (e.g., lists of digits, words or unfamil- initially presented more global language impairment iar words) and/or visuospatial patterns (e.g., object patients who presented specific language impairment, copying, spatial sequence reproduction). Given the im- childhood aphasia, or epileptic childhood aphasia portance of short-term memory as a first step toward (Landau-Kleffner syndrome) during childhood can long-term learning of new information, these children show relatively good language recovery at adulthood will typically also have difficulties in learning new but verbal short-term memory impairment will still be verbal information such as a new vocabulary, new present(Majerusetal.,2004). definitions, and in learning associations between A number of genetic syndromes are also character- p0045 abstract concepts as for example needed in chemistry ized by poor short-term memory spans, either for verbal (Baddeley et al., 1998). Furthermore given the implica- short-term memory, such as in Down syndrome (trisomy tion of short-term memory during mental calculation 21) or for visual short-term memory, such as in and reasoning, difficulties will also be observed in ar- Williams syndrome (7q11.23) and X-related syndromes ithmetic and sentence comprehension. The deficit can (Fragile X, Turner syndrome, Klinefelter syndrome, be selective for verbal or visual information, or involve and Rett syndrome). Velo-cardio-facial syndrome both modalities. Although short-term memory deficits (microdeletion 22q11.21) is particularly interesting here do not prevent successful completion of primary and since a specific deficit for the retention of order secondary school education, they will nevertheless information has been observed: affected children can ac- cause a significant handicap by slowing the affected curately maintain and reproduce the items (e.g., child’s learning rate and his/her comprehension of words, digits) that have been presented to them but they the explanations and task assignments provided by will have more important difficulties in maintaining the teaching staff. and reproducing the order in which the items have been p0035 The observation of a selective short-term memory im- presented (Majerus et al., 2007). Recent studies pairment, in the absence of any other cognitive deficit, is suggest indeed that one of the major functions of extremely rare. This is partly due to the fact that short- short-term memory is to maintain the order of events term memory deficits are the consequence of lesions in that just occurred, the events themselves being directly the inferior parietal lobule and/or the inferior frontal gy- coded via temporary activation of the respective long- rus, most often as a result of a cerebrovascular accident term knowledge bases (i.e., the language system for ver- in the territory of the left middle cerebral artery. This bal information) (Majerus, 2009). Finally, we should kind of accident is rare in children. Furthermore, trau- note that in Fragile X syndrome, the short-term memory matic brain injury, more common in populations of chil- impairment is typically more general, including poor dren, rarely leads to focal and selective lesions in these retention for verbal, visual, and order information, areas, although short-term memory disorders are a fre- most likely related to more fundamental attentional dif- quent consequence of traumatic brain injury in associa- ficulties during encoding of information in short-term tion with other memory impairments (episodic memory). memory.

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MEMORY DISORDERS IN CHILDREN 3 s0015 EPISODIC LONG-TERM MEMORY More subtle and strategic deficits during memory p0065 DISORDERS retrieval have been observed in children presenting with attention-deficit/hyperactivity disorder (ADHD). p0050 Children presenting with episodic memory deficits will Cornoldi and colleagues (1999) observed deficits in 12- have difficulties explicitly learning and/or retrieving year-old children with ADHD in a picture task new information and its associated spatiotemporal con- when no information about possible encoding strategies text. These children will forget appointments, tasks-to- was given (such as regrouping the pictures according to do, and activities they had the same day or several their semantic category). However, recall performance days/weeks ago. This will also reduce their ability to pro- was normalized when the children were informed about ject into the future and to design future plans/activities. the strategy and were trained to use it, indicating that the If there was an acute onset of memory difficulties, mem- memory deficits in ADHD are characterized by difficul- ories that have been learned before the onset will gener- ties in implementing accurate encoding and retrieval ally remain intact and will continue to be retrieved strategies, rather than impairment at the level of consol- accurately. Furthermore, the deficit can be characterized idation. In the same vein, premature birth is a further risk either by difficulties during encoding (information is not factor for developing episodic memory disorders, al- correctly encoded in episodic memory), during consoli- though the impairments may be relatively subtle and dation (high rate), and/or during retrieval not significant in all children born preterm. (information cannot be retrieved but if correct retrieval Finally, episodic memory deficits are also observed in p0070 cues are provided, performance can be improved). a range of genetic disorders such as Rett syndrome, Kli- Although these children will show important difficulties nefelter syndrome, Down syndrome, velo-cardio-facial in remembering everyday activities, learning of semantic syndrome, and Williams syndrome, the two latter and procedural information via repeated exposure is syndromes being characterized by an impairment nevertheless possible. Hence these children can evolve especially for visual episodic memory. in a standard educational setting in a satisfactory man- ner, but episodic aspects of learning will be poor or OTHER MEMORY DISORDERS s0020 impossible. p0055 A frequent cause of selective episodic memory defi- Semantic memory disorders will lead to deficient factual p0075 cits, leading to a pattern of developmental , are knowledge and poor semantic categorization (e.g., Do lesions to the bilateral hippocampal areas as a result of “cat” and “dog” belong to the same semantic category?), anoxia, ischemia, or carbon monoxyde poisoning. These while categorization based on phonological information lesions will particularly affect the consolidation stage of will be possible (e.g., rhyme judgment). Vocabulary episodic memory. In some cases, recognition memory knowledge will also be poor while other language aspects can be relatively preserved, as opposed to full, uncued will be preserved. In children, semantic memory disor- recall. If these lesions occur at a very early age (i.e., at ders are less frequently observed, relative to episodic the perinatal stage), the difficulties in episodic memory or short-term memory disorders. They are typically the may be observable only 3 to 4 years later, when episodic consequence of lesions to the medial and lateral inferior memory starts to get recruited more extensively. In some , even in the absence of damage to the cases, the episodic memory deficit may be restricted to hippocampal area (Temple and Richardson, 2006). the verbal or the visual condition (Temple and Although semantic memory disorders have been less Richardson, 2006). intensively investigated, they appear in children present- p0060 Other causes leading to episodic memory deficits are ing with late-onset temporal lobe epilepsy, especially traumatic brain injury (in about 50% of children with left mesial temporal lobe epilepsy, although memory im- traumatic brain injury), brain tumors (especially those in- pairment is less frequent than it is in adults presenting volving the third ventricle), and cerebrovascular acci- with the same type of epilepsy (see also Jambaque´ & dents. Epileptic disorders, especially those involving Lassonde, this volume). More generally, impaired the medial temporal lobes, are a further frequent cause semantic memory characterizes a number of genetic of episodic memory deficits. If the epileptic foci are syndromes associated with mental retardation, such as unilateral, the memory deficits may be restricted to Williams syndrome, Down syndrome, and Fragile X. verbal (left temporal) or visual (right temporal) informa- Finally, difficulties in are charac- p0080 tion, although more general deficits are observed when terized by various difficulties in learning new sensorimo- the foci are bilateral (Temple, 2002). It is important to tor skills, such as those involved in becoming a skilled note that even a single status epilepticus can lead to music player, a skilled reader, or a skilled speaker. These alterations in the hippocampal regions 5 days after onset difficulties are very rarely observed as a result of acquired (Scott et al., 2002). brain lesion but may occasionally appear during epileptic

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4 S. MAJERUS AND M. VAN DER LINDEN t0005 Table 27.1

Synopsis of memory impairments, associated syndromes, and associated cerebral/genetic anomalies

Memory system Symptoms Syndromes Brain lesions/genetic anomaly

Short-term memory Verbal Inability to maintain for a few Developmental STM disorder None seconds new verbal information; difficulties in TBI, CVA , epileptic L posterior temporal/L acquiring a new vocabulary syndromes inferior frontal

Down syndrome Trisomy 21 Fragile X Xq27.3 mutation

Order Difficulties in maintaining the Velo-cardio-facial syndrome 22q11.2 microdeletion order of events

Visual Inability to maintain for a few Traumatic brain injury or CVA R parieto-occipital seconds new visual information; difficulties in Williams syndrome 7q11.23 microdeletion mental imagery Fragile X Xq27.3 mutation Turner syndrome 45X0, 47XXX Klinefelter syndrome 47XXY, 47XYY, 48XXXY Rett syndrome Xq28 mutation

Episodic memory Inability to learn new Developmental amnesia Bilateral hippocampi information and its spatiotemporal context; Mesial temporal lobe epilepsy L and/or R increased forgetting of past and future events TBI Dorso-lateral prefrontal cortex; diffuse axonal injuries Brain tumor, CVA 3rd ventricle

Down syndrome 21 trisomy Williams syndrome 7q11.23 microdeletion Velo-cardio-facial syndrome 22q11.2 microdeletion Klinefelter syndrome 47XXY, 47XYY, 48XXXY Rett syndrome Xq28 mutation

Semantic memory Inability to learn factual Temporal lobe epilepsy L lateral inferior and medial information; poor temporal lobe vocabulary knowledge Williams syndrome 7q11.23 microdeletion

Procedural memory Difficulties to learn Temporal lobe epilepsy Cerebellar involvement sensorimotor skills (speech, Williams syndrome 7q11.23 microdeletion reading, music playing, Specific language impairment? None keyboard typing) Dyslexia? None

CVA, cerebrovascular accident; STM, short-term memory; TBI, traumatic brain injury; L, left; R, right.

disorders, especially if the is involved, as sug- procedural memory disorders, as tested by serial reaction gested by a study in adult epileptic patients (Hermann time tasks, possibly related to abnormal development of et al., 2004). On the other hand, genetic syndromes such basalnucleiwhichareinvolvedinprocedurallearning. as Williams syndrome have been associated with More generally, the difficulties in learning to speak in

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MEMORY DISORDERS IN CHILDREN 5 specific language impairment and in learning to write in Baddeley AD, Gathercole SE, Papagno C (1998). The phono- dyslexia have been suggested to reflect impairment in pro- logical loop as a language learning device. Psychol Rev cedural memory, preventing the automatization of the 105: 158–173. complex auditory-motor and visual-motor loops involved Cornoldi C, Barbieri A, Gaiani C et al. (1999). Strategic mem- in the production of oral and written language, respec- ory deficits in attention deficit disorder with hyperactivity participants: the role of executive processes. Dev tively (Ullman and Pierpoint, 2005). Neuropsychol 15: 53–71. Hanten G, Martin RC (2001). A developmental phonological

s0025 CONCLUSIONS short-term memory deficit: A case study. Brain Cogn 45: 164–188. p0085 This chapter provides an overview of the main memory Hermann B, Seidenberg M, Sears L et al. (2004). Cerebellar disorders encountered in neuropediatric populations atrophy in temporal lobe epilepsy affects procedural mem- (see also Table 27.1). Although we have presented the dif- ory. Neurology 63: 2129–2131. ferent disorders as separate entities, some of these can Majerus S (2009). Verbal short-term memory and temporary co-occur. For example, lesions to the medial temporal activation of language representations: the importance of distinguishing item and order information. In: A Thorn, lobe often lead to both semantic and episodic memory M Page (Eds.), Interactions between short-term and long- deficits, depending on the extent of the lesion and the in- term memory in the verbal domain. Psychology Press, volvement or not of hippocampal areas. Similarly, im- Hove, UK, pp. 244–276. pairments in short-term memory and episodic memory Majerus S, Van der Linden M, Poncelet M et al. (2004). Can frequently co-occur in children suffering from trau- phonological and semantic short-term memory be dissoci- matic brain injury. Moreover, the different memory sys- ated? Further evidence from Landau-Kleffner Syndrome. tems interact: although semantic memories can be Cognitive Neuropsychology 21: 491–512. learned while episodic memory is significantly impaired, Majerus S, Van der Linden M, Braissand V et al. (2007). a joint intervention of both systems will lead to the fast- Verbal short-term memory in children and adults with est learning rate of new information. Similarly, the codes a chromosome 22q11.2 deletion: a specific deficit in used in short-term memory tasks are shared with long- serial order retention capacities? Am J Ment Retard 112: 79–93. term memory systems: semantic information in a Majerus S, D’Argembeau A, Martinez Perez T et al. short-term memory task will be stored by first activating (2010). The commonality of neural networks for verbal corresponding information in long-term semantic mem- and visual short-term memory. J Cogn Neurosci 22: ory. Hence, a deficit in one memory system will also im- 2570–2593. pact on other memory systems. Future studies will need Scott RC, Gadian DG, King WK et al. (2002). Magnetic reso- to determine the precise mechanisms that allow these in- nance imaging findings within 5 days of status epilepticus teractions between memory systems and how these inter- in childhood. Brain 125: 1951–1999. actions can be affected via brain pathology. Temple C (2002). Developmental and acquired am- nesias of childhood. In: AD Baddeley, MD Kopelman, REFERENCES BA Wilson (Eds.), The Handbook of Memory Disorders. Wiley, Chichester, pp. 521–542. Baddeley AD (1993). Short-term phonological memory and Temple CM, Richardson P (2006). Developmental amnesia: long-term learning: A single case study. European Fractionation of developing systems. Cognitive Journal of Cognitive Psychology 5: 129–148. Neuropsychology 23: 762–788. Baddeley AD, Wilson BA (1993). A developmental deficit in Ullman MT, Pierpoint EI (2005). Specific language impair- short-term phonological memory: implications for lan- ment is not specific to language: the procedural deficit hy- guage and learning. Memory 1: 65–78. pothesis. Cortex 41: 399–433.

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Non-Print Items

ABSTRACT

Memory disorders are a frequent consequence of a variety of childhood neurological conditions. We will review the characteristics of memory disorders as a function of the main four memory systems: short-term memory, episodic memory, semantic memory, and procedural memory. For each system, we will identify the most typical cerebral and/or genetic correlates, and we will discuss the impact of impairment of each memory system on everyday life functioning.

HCN, 978-0-444-52891-9

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