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Child Neuropsychology: A Journal onNormal and Abnormal Development inChildhood and AdolescencePublication details, including instructions for authors andsubscription information:http://www.tandfonline.com/loi/ncny20

Working Memory In Individuals WithFragile X SyndromeSilvia Lanfranchi a , Cesare Cornoldi b , Sibilla Drigo c & RenzoVianello aa University of Padova, Department of Developmental Psychology,Padova, Italyb University of Padova, Department of General Psychology, Padova,Italyc University of Padova, Padova, ItalyPublished online: 10 Mar 2009.

To cite this article: Silvia Lanfranchi , Cesare Cornoldi , Sibilla Drigo & Renzo Vianello (2009) WorkingMemory In Individuals With Fragile X Syndrome, Child Neuropsychology: A Journal on Normal andAbnormal Development in Childhood and Adolescence, 15:2, 105-119

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Child Neuropsychology, 15: 105–119, 2009http://www.psypress.com/childneuropsychISSN: 0929-7049 print / 1744-4136 onlineDOI: 10.1080/09297040802112564

© 2008 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

WORKING MEMORY IN INDIVIDUALS WITH FRAGILE X SYNDROME

Silvia Lanfranchi,1 Cesare Cornoldi,2 Sibilla Drigo,3 and Renzo Vianello4

1University of Padova, Department of Developmental Psychology, Padova, Italy,2University of Padova, Department of General Psychology, Padova, Italy,3University of Padova, Padova, Italy, and 4University of Padova, Department ofDevelopmental Psychology, Padova, Italy

The present research tests the hypothesis that fragile X syndrome (FXS) is associated with adeficit in working memory (WM) and the deficit is more pronounced the higher the controlrequirements of the task. To this purpose, 15 boys with FXS and 15 typically developingchildren, matched for mental age, assessed with Logical Operation Test, were tested withbatteries of 4 verbal and 4 visuospatial WM tasks requiring different levels of control.Children with FXS showed a performance equal to controls, in WM tasks requiring low andmedium-low control but significant impairment in correspondence with greater controlrequirements. Results show that boys with FXS present a WM deficit only when high controlis required by the task, supporting the hypothesis that control can be a critical variabledistinguishing WM functions and explaining intellectual differences. On the contrary thehypothesis that the FXS is associated with a visuospatial deficit was not supported.

Keywords: Working memory; Verbal memory; Visuospatial memory; Fragile X syndrome;Intellectual disability.

INTRODUCTION

There is great debate concerning the relationship between working memory anddevelopmental disabilities (for a review, see Swanson & Siegel, 2001). In general, researchershave shown that children with various cognitive developmental disabilities performpoorly on working memory tests. In particular, evidence on working memory abilities inneurogenetic disorders has shown that these failures may present varying patterns ofperformance, suggesting that working memory is divided into different components thatcan be tapped by different working memory tasks. In this context, Baddeley’s (1986)model has been used to show that some children may have specific difficulties in tasksconcerning the linguistic component of working memory (the Articulatory Loop), whereasothers may fail in one or both of the other two components (i.e., the Visuospatial Sketchpadand the Central Executive). The model may explain different types of working memoryperformance associated with varying genotypes, and in particular the superior performanceof children with Williams syndrome over children with Down syndrome on Articulatory

Address correspondence to Dr. Silvia Lanfranchi, University of Padova, Department of DevelopmentalPsychology, via Venezia 8, Padova, 35131 Italy. E-mail: silvia.lanfranchi@unipd.it

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106 S. LANFRANCHI ET AL.

Loop tasks and the opposite pattern of performance on Visuospatial Sketchpad tasks(e.g., Jarrold, Baddeley, & Hewes, 1999; Marcell & Weeks, 1988; Wang & Bellugi, 1994).

Evidence concerning the Central Executive drawn from studies of neurogeneticdisorders is less clear and has been interpreted in differing ways. In particular, Cornoldiand colleagues (Cornoldi, Rigoni, Venneri, & Vecchi, 2000; Cornoldi & Vecchi, 2003)refined the Baddeley model in order to offer a more detailed specification of differences inworking memory abilities, particularly for children with cognitive developmental disabilitiesand neurogenetic disorders. According to Cornoldi and Vecchi, some working memorytasks cannot be considered related to the content-specific low-attention working memorysubsystems, i.e., Articulatory Loop or Visuospatial Sketchpad, as they require active controlon maintained information. However they cannot be related to the Central Executive aswell, as they maintain content specificity, but they must be considered examples of taskssharing some characteristics both with the content subsystems and the Central Executive.According to Cornoldi, Carretti, and De Beni (2001), highly intelligent children withspecific learning disabilities should fail mainly in low-control tasks; children with readingcomprehension and/or problem-solving difficulties (e.g., Passolunghi, Cornoldi, &De Liberto, 1999) may have problems at a somewhat higher level of control (e.g., at anintermediate level of control, when selection and inhibition of specific verbal informationis required), whereas children with intellectual disabilities may fail at an even higher levelof control, as supported by evidence concerning individuals with mental retardation(Lanfranchi, Cornoldi, & Vianello, 2002) and, more specifically, with Down syndrome(Lanfranchi, Cornoldi, & Vianello, 2004; Vicari, Carlesimo, & Caltagirone, 1995).

The present study examines the case of fragile X syndrome (FXS) and tests thehypothesis that individuals with this syndrome present a working memory deficit onlyassociated with high-cognitive tasks, but in contrast with individuals with Down syndrome,their deficit is comparable for both visuospatial and verbal tasks.

In the past few years many studies have been conducted to define the cognitivephenotype of FXS, an X-linked genetic disorder affecting approximately 1/4000 malesand 1/8000 females (Turner, Webb, Wake, & Robinson, 1996) representing the mostcommon inherited identifiable cause of learning disability and intellectual disabilities. Thesyndrome is characterized by different levels of intellectual disability; most cases varyingbetween moderate and severe (Dykens, Hodapp, & Finucane, 2000). A particularneurocognitive profile has been hypothesized for this syndrome (Einfeld, Tonge, & Florio,1994; Freund, Reiss, & Abrams, 1993; Turk, 1992; Warren & Ashley, 1995). The profileseems to vary somewhat between males and females. The cognitive profile in malesshows relative strengths in language, simultaneous information processing, and faceand emotion recognition (Hodapp, Dykens, Ort, Zelinsky, & Leckman, 1991; Turk &Cornish, 1998). In contrast, males with FXS show a relative weakness in visuospatialcognition (Cornish, Munir, & Cross, 1999; Freund & Reiss, 1991), and in sequentialinformation processing, in reproduction of items in a serial or temporal order (Cornish,Turk, Wilding, Sudhalter, Munir, Kooy, & Hagerman, 2004; Jakala et al., 1997; Wilding,Cornish, & Munir, 2002).

Females with the disorder typically score within the mildly mentally retarded rangeor normal cognitive range but also manifest learning disabilities, most often in mathematicaltasks (Riddle et al., 1998). Neuropsychological testing reveals that females with thiscondition have a higher verbal than performance IQ and frontal lobe-related deficits(Borhgraef, Umans, Steyaert, Legius, & Fryns, 1996; Hagerman & Sobesky, 1989; Jakalaet al., 1997; Mazzocco, Hagerman, Cronister-Silverman, & Pennington, 1992).

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WORKING MEMORY IN FRAGILE X SYNDROME 107

As regards the working memory components, some studies have found deficits inboth verbal and visuospatial short-term memory in males with FXS (Cornish, Munir, &Cross, 2001; Dykens, Hodapp, & Leckman, 1987; Freund & Reiss, 1991; Jakala et al.,1997; Munir, Cornish, & Wilding, 2000). For example, Munir et al. (2000) found thatindividuals with FXS performed significantly worse than controls matched for mental ageon a nonword span task, a forward digit span task, a spatial memory task, and a backwarddigit span task. The study also suggested that the memory profile for individuals with FXSmay be strongly determined by the nature of the to-be-remembered material and thatinformation presented in a meaningful context may be more accurately recalled than moreabstract information; in fact individuals with FXS performed better (i.e., comparable tosame mental-age controls) in story-retelling tasks and worse (also significantly lower thanindividuals with Down syndrome) in a nonword span task (Maes, Fryns, Van Walleghem, &Van den Berghe, 1994).

Furthermore, there is contradictory evidence concerning the fact that FXS is associatedwith a selective deficit in visuospatial short-term memory as opposed to verbal short-termmemory. Shapiro et al. (1995) found that adult males with FXS performed at a comparablelevel to adult males with Down syndrome on the forward digit span but performed worseon measures of visuospatial short-term memory. This may be in accordance with Freundand Reiss’s (1991) hypothesis that the cognitive profile of males with fragile X syndromeshows relative strengths in verbal tasks and relative weaknesses in visuospatial tasks.However, the choice by Shapiro et al. (1995) to compare individuals with FXS with individualswith Down syndrome rather than with typically developing individuals can be criticized:in fact many studies reported that individuals with Down syndrome have a lower perfor-mance compared to typically developing children, matched for mental age, on verbalworking memory tasks, whilst their visuospatial working memory is relatively preserved(e.g., Jarrold & Baddeley, 1997, 2001). For this reason it is possible that males with FXSnot only have a visuospatial but also a verbal working memory impairment, as has beensuggested by some studies (Cornish et al., 2001; Dykens et al., 1987; Freund & Reiss,1991; Jakala et al., 1997; Munir et al., 2000).

Furthermore, there are several studies showing that deficits at higher levels of attentioncontrol/executive functioning, which involve switching attention, inhibiting repetitiousbehavior, planning and organizing, affect boys (Munir et al., 2000; Scerif, Cornish, Wilding,Driver, & Karmiloff-Smith, 2004; Wilding et al., 2002) and adult males (Cornish et al.,2001) with FXS. This impairment was found also in girls (Kirk, Mazzocco, & Kover, 2005)and in women (Mazzocco, Hagerman, & Pennington, 1992; Mazzocco, Pennington, &Hagerman, 1993) with FXS. Some authors suggest that a working memory and executivefunction deficit underlie deficits in other areas such as the difficulty experienced bywomen with FXS on discourse tasks (Simon, Keenan, Pennington, Taylor, & Hagerman,2001) or the mathematical difficulties experienced by girls with FXS (Mazzocco, 1998).For the same reason it may be useful to improve our knowledge about working memory inindividuals with FXS.

In conclusion, FXS seems characterized by specific working memory deficits, butthe pattern of deficit remains unclear, since different studies have reached differentconclusions. This is in part due to the necessarily small samples in most of the studies, andin part to the varied methods used.

The aim of this study was to analyze verbal and visuospatial working memorycharacteristics, at different levels of control, in boys with FXS. In accordance withCornoldi and Vecchi (2003), control was defined on the basis of the degree of cognitive

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active processing required to manipulate information maintained in a temporary memorysystem. Control may range from simple maintenance to complex order change, selection,inhibition, and transformation processes and finally, at the higher end of the scale, dualprocessing. In order to assess working memory performance, at different levels of control,in individuals with mental retardation, Lanfranchi et al. (2004), in a previous study withindividuals with Down syndrome, created a series of four verbal and four visuospatialtasks. In order to have simple and comparable tasks, appropriate for children with lowmental ages, Lanfranchi et al. (2004) reduced the quantity of material in the tasks requiringa higher degree of control and simplified the procedure. In fact, with the same quantity ofmaterial and other aspects held constant, an increase in required control should increase taskdifficulty. The verbal and visuospatial components of working memory were defined notonly on the basis of how the corresponding tests were presented (oral presentation for verbalworking memory and visual for visuospatial working memory) but also on the basis of thestimulus properties (words for verbal working memory and locations/spatial configurationsfor visuospatial working memory). The tasks were analyzed with respect to their processingand psychometric properties and it emerged that they involved different aspects of workingmemory and the majority of the reliability coefficients were within an acceptable range forbasic research, around .70 (Lanfranchi et al., 2004).

In their study, Lanfranchi et al. (2004) obtained two main results, i.e., that individualswith Down syndrome performed more poorly than typically developing (TD) children incorrespondence with an increase in the required degree of control, and that they performedcomparatively worse on verbal tasks than on visuospatial tasks.

On the basis of these results and a number of studies of individuals with FXS(Cornish et al., 2001; Kwon et al., 2001; Mazzocco et al., 1993; Munir et al., 2000; Munir,Cornish, & Wilding, 1998), we would expect that in the present study the required degreeof control will differentiate children with FXS and TD children and that children withFXS will perform on a par with typically developing children on low-control tasks butshow a poorer performance in high-control tasks.

A second aim of the study was to determine whether the working memory of indi-viduals with FXS is affected by the type of material (visuospatial versus verbal) presented.

By testing working memory in individuals with FXS, we can analyze the workingmemory profile associated with this syndrome and which aspects might be specific to fragileX syndrome and which might be linked to intellectual disabilities. It was hypothesizedthat, if there is a general association between intellectual disabilities and a deficit in workingmemory control, individuals with FXS would also present the same type of working memorycontrol deficit found in individuals with Down syndrome. However, in contrast withchildren with Down syndrome, individuals with FXS were not expected to show anincreased deficit in verbal working memory tasks, but rather a similar difficulty on verbaland visuospatial tasks or even a greater difficulty on the latter, if observations by Shapiroet al. (1995) can be applied to the present context.

METHOD

Participants

Participants were 15 boys with fragile X syndrome, with a mean chronologicalage (CA) of 12 years and 9 months (SD = 3.9 years), ranging from 6 years and 11 monthsto 18 years and 5 months, and with a mean mental age (MA) of 5 years and 2 months

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WORKING MEMORY IN FRAGILE X SYNDROME 109

(SD = 8 months), ranging from 4 years and 11 months to 6 years and 8 months. Thecontrol group included 15 typically developing boys, with a mean chronological age of4 years and 11 months (SD = 8 months), ranging between 4 years and 1 month and 6 yearsand 4 months, and with a mean mental age of 5 years and 2 months (SD = 8 months), rangingbetween 4 years and 11 months and 6 years and 8 months.

Groups were individually matched to within 3 months, on MA, on the basis of theirscores on the Logical Operations test (Vianello & Marin, 1997), an intelligence test thatprovides a MA measurement in terms of logical thinking development and locates a childwithin three-month ranges of mental age. This test seems particularly suitable for childrenwith intellectual disabilities. It is inspired by the Piagetian theory of operatory thinkingand includes 18 tasks that assess the following areas of logical thinking: seriation, numer-ation, and classification. In comparison with traditional Wechsler intelligence scales (thecorrelation of the Wechsler Intelligence Scale for Children with the Logical Operationstest is .68), the Logical Operations test is less affected by cultural and verbal components.In comparison with the Columbia Mental Maturity Scale (r = .78), the Logical Operationstest is less affected by visuospatial components. This test, therefore, seems particularlyappropriate for matching children with FXS to typically developing children on a centralintelligence aspect and logical thinking, whilst limiting the influence of culture, linguisticability, and visuospatial components (for a review, see Vianello & Marin).

Tasks

The working memory tasks were those used by Lanfranchi et al. (2004) and werebased on a definition of the degree of required control. It should be noted that, if differentrequired control was associated with the same quantity of to be-memorized material,the prediction was that the task difficulty increased, and the typical score decreased, incorrespondence with increases in control. For this reason, the tasks were constructed inorder to produce similar scores in typically developing 5-year-old children, as the quantityof to-be-memorized material decreases in correspondence with increases in the requiredcontrol, thus controlling for the effect of task difficulty. In this way, any difference relatedto control could not be attributed to a difference in test difficulty and discriminativepower. Each task was preceded by instructions and practice trials with one or more shortlists. The experimental phase started only if the child appeared to have understood thenature of the task, responding correctly on a practice trial. All the children understoodthe tasks, and no one was excluded. Each task moved progressively from the shortest tothe longest list, with two lists of the same length for each trial. However, to avoid frustratingand difficult situations, and in accordance with a rule used in the Wechsler IntelligenceScale for Children-Revised (WISC-R; Wechsler, 1974) digit span task, every single taskwas interrupted if the child failed on both lists of the same length and the remaining itemswere considered incorrect. Task order within each session was randomly defined for eachparticipant.

For the complete task descriptions see Lanfranchi et al. (2004).

Verbal Working Memory Tasks. Four verbal WM tests varying in requiredcontrol, but similar in difficulty, were administered. Task 1 required the lowest control,task 4 the highest. A forward word span task was considered to be a low-control workingmemory task; a backward word span task was assumed to require a little greater controlbecause the child would have to perform a simple operation on the material (i.e., reverse

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110 S. LANFRANCHI ET AL.

the word order). A selective word recall task (inspired by classical working memorylistening — reading span tasks, e.g., Daneman & Carpenter, 1980) would require evengreater control because the child has to select some information and control interferencefrom information that has become irrelevant. In previous studies and analyses, researchershave found evidence to show that central working memory components are involved in theverbal working memory span (e.g., Baddeley, 1986; Bayliss, Jarrold, Gunn, & Baddeley,2003). However, the task has been shown to maintain verbal specificity typical of tasksintermediate between a simple span and a central control task (Cornoldi & Vecchi, 2003).A dual request task was considered to be the highest control task because it not onlyrequires operations similar to those of the previous task but also involves a dual taskrequirement. Baddeley suggested that a dual task requirement is a typical feature of situationsinvolving the most controlled operations of working memory associated with the centralexecutive component of such a memory system. In our particular case the second taskdid not have to be performed concurrently with the first (as in other typical dual tasksituations), but only when a stimulus with particular properties was presented. This addi-tional request was considered to be the highest control task because it was combined withthe request already present in the selective word recall task.

All four tests used the same material, i.e., 11 two-syllable words, with high values ofconcreteness and familiarity. In all, tasks words were presented verbally by the experi-menter at the rate of one word per second. The experimenter was trained to carry out astandard presentation, keeping the rate and tone of voice constant.

Task 1 (low control) forward word recall. The child was presented with lists of twoto five words and was required to repeat the list immediately and in the same order aspresented.

Task 2 (medium-low control) backward word recall. The child was presented withlists of two to five words and was required to repeat each list in reverse order immediatelyafter presentation.

Task 3 (medium-high control) selective word recall. The child was presented withone or two lists of words and was required to repeat the first word of each list after thepresentation of the entire set of materials.

Task 4 (high control) verbal dual task. The child was presented with a list of two tofive words and was asked to remember the first word on the list and to tap on the tablewhen the word PALLA (ball) was presented.

Visuospatial Working Memory Task. Four visuospatial WM tasks were alsoadministered involving different levels of control, but implying a similar degree of diffi-culty. The required control level increased from the first task, which required the leastcontrol, to the fourth, which required the highest control. The adapted version of the Corsitask represented the most passive task (see also Cornoldi & Vecchi, 2003) because partic-ipants simply have to repeat a sequence of positions just presented in the same format.Furthermore, despite the fact that performance in the forwards and backwards Corsi taskmay be somewhat similar, suggesting a similar degree of difficulty, it seems that requiredcontrol in the backwards version is slightly higher, as the child has to reverse the positionorder (Cornoldi & Vecchi). A medium-high-control task required the selective recall of

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WORKING MEMORY IN FRAGILE X SYNDROME 111

the first positions of sequences of positions (in the parallel verbal memory task the childwas required to remember the first word of each string). Finally, the highest control taskmade the same request as the previous task but also included a dual task request: partici-pants had to tap on the table when the red cell of the experimental matrix was indicated.

For these tasks we used 3 × 3 or 4 × 4 white chessboards and two small plastic frogs.

Task 1 (low control) pathway forward. We showed the child a path taken by asmall frog on a 3 × 3 or 4 × 4 chessboard. The child had to remember the pathway imme-diately after presentation, by moving the frog from cell to cell, just as the experimenterhad done. There were four levels of difficulty depending on the number of steps in thefrog’s pathway and the dimensions of the chessboard (3 × 3 at the first level with twosteps, and 4 × 4 in the other levels, with two, three, and four steps, respectively). Stepswere presented at the rate of approximately one step every 2 seconds.

Task 2 (medium-low control) pathway backward. We showed the child a frog’spath on a 3 × 3 or 4 × 4 chessboard, in the same way as in the pathway forwards task. Thechild had to remember the path in reverse order. There were four levels of difficulty,depending on the number of steps in the frog’s path and the size of the chessboard (3 × 3 inthe first and second level, and 4 × 4 in the other levels). Each level had two series of items.

Task 3 (medium-high control) starting position selection. We showed the child oneor two frog’s paths on a 4 × 4 chessboard, in the same way as before. The child had toremember the frog’s starting positions. The task had four different levels of difficulty,depending on the number of pathways and the number of steps in each pathway. At levelone and two respectively we administered one pathway with two steps and one with threesteps. At the levels three and four we presented two pathways, respectively with two andthree steps.

Task 4 (high control) visuospatial dual task. The child had to remember the frog’sstarting position on a pathway on a 4 × 4 chessboard (where one of the 16 cells was coloredin red). He also had to tap on the table when the frog jumped onto the red square. The taskhad four different levels of difficulty, according to the number of steps in the pathway:two, three, four, and five steps, respectively.

In scoring all tasks, following a simple rule frequently adopted in the field(e.g., Peterson & Peterson, 1959), we only considered a trial correct if the child recalledthe complete set of material and, for the dual request tasks, also tapped correctly. There-fore, since all the tasks had eight trials, the minimum possible score for every task was 0and the maximum one was 8, with the further advantage of making the tasks more easilycomparable.

PROCEDURE

In a first section participants completed the Logical Operation test. The raw score ofthis test for each individual with FXS was used to identify the matched child of the controlgroup. Subsequently, the participants completed the four verbal and four visuospatialworking memory (WM) tasks. All these tasks were administered individually in two sessionsseparated by approximately 1 week, with each session lasting approximately 20 minutes.The order of presentation of the tasks was counterbalanced across participants.

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112 S. LANFRANCHI ET AL.

RESULTS

The reliability for tasks 1, 2, 3, and 4 (Cronbach alpha coefficients, as a measure ofhomogeneity between trials in every task) were acceptable, although lower than in precedingstudies, probably also because of the restricted distributions of the scores, i.e., respectively:.52, .74, .71, and .79 for verbal tasks and .41, .79, .72, and .88 for visuospatial tasks. (Notethat the lowest coefficients were found for tasks, such as the word span and the pathwaymemory ones, which have been widely used in the field and have demonstrated theirusefulness for the study of cognitive deficits.)

Tables 1 and 2 present the mean (and standard deviation) number of successful trialsfor the four tasks respectively in verbal and visuospatial tasks. An inspection of the tables

Table 1 Verbal Working Memory—Mean Numbers (and SDs) of Trials, in Which Participants with FragileX Syndrome (FXS) and Typically Developing Children (TD) Were Correct. Values of the Student’s t- andMann-Whitney’s U-Comparisons are Reported.

Task Group N Mean SD Diff. means t U

Forward word recall TD 15 3.93 0.59 0.07 0.18 106FXS 15 3.87 1.30

Backward word recallTD 15 3.33 1.84 0.87 1.66 86.5FXS 15 2.47 0.83

Selective word recall TD 15 4.67 1.11 1.40 2.53* 53*FXS 15 3.27 1.83

Verbal dual task TD 15 4.2 1.93 1.8 2.66** 52*FXS 15 2.40 1.76

*p £ .05; **p £ .01.

Table 2 Visuospatial Working Memory—Mean Numbers of Trials (and SDs) Where Participants with Fragile XSyndrome (FXS) and Typically Developing Children (TD) Were Correct. Values of the Student’s t- and Mann-Whitney’s U- Comparisons are Reported.

Task Group N Mean SD Diff. means t U

Pathway forwardTD 15 5.27 1.10 0.73 1.75 76FXS 15 4.53 1.19

Pathway backwardTD 15 5.00 1.31 0.87 1.19 98.5FXS 15 4.13 2.50

Starting positionTD 15 4.67 1.95 2.00 3.27** 48.5**FXS 15 2.67 1.35

Visuospatial dual taskTD 15 4.80 2.98 2.60 2.49** 51.5**FXS 15 2.20 2.73

*p ≤ .05; **p ≤ .01.

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WORKING MEMORY IN FRAGILE X SYNDROME 113

shows that the performance of the control group both in the verbal and visuospatial taskswas substantially similar, confirming the assumption of Lanfranchi et al. (2004) thatincreased control was not associated with increased difficulty for typically developingchildren.

The results were analyzed in the following order. We first computed an omnibusMANOVA considering all the variables together. Then we compared the two groups foreach test. Finally we examined within the two groups the trend related to increases inrequired control. A 4 (tasks) × 2 (verbal/visuospatial) × 2 (groups) MANOVA showed asignificant effect of tasks, F(3, 84) = 4.214, p = .008, η2 = .13, of groups, F(1, 28) = 9.82,p = .001, η2 = .26, and of verbal/visuospatial distinction, F(1, 28) = 10.865, p = .003,η2 = .28, because, in general, participants had higher performance in visuospatial than inverbal tasks. Despite this result the interactions for verbal/visuospatial × group and fortasks × verbal/visuospatial x group were not significant, respectively, F(3, 84) = 1.761,p > .05, η2 = .06 and F(3, 84) = 0.271, p > .05, η2 = .01. These results show that in bothgroups there were no differences between performance on verbal and visuospatial tasksrequiring the same level of control. This means that in individuals with FXS there were nodifferences between performance on verbal and in visuospatial working memory tasks.Moreover, we found a significant interaction for tasks × groups, F(3, 84) = 4.24, p = .008,η2 = .132.

To better investigate the latter result, separate comparisons between groups for thefour verbal and visuospatial tasks were made using parametric statistics (Student’s t-test).Due to the limited range of scores, we decided to also compute nonparametric statistics(Mann-Whitney’s U-test). As shown in Table 1 all the analyses revealed that the twogroups were significantly different in selective word recall and in verbal dual task, requiringmedium-high and high control respectively, but not in forward and backward word recalltasks, requiring low and medium-low control. Moreover, the differences between themeans of the two groups increased in correspondence with increases in the degree ofcontrol required by the tasks.

The hypothesis of a control continuum was also tested with a trend analysis with thedegree of required control as the independent variable. Trend analysis of the gap betweengroups corresponding to an increase in control showed a positive relationship between thetwo aspects. This relationship can be represented by a positively inclined straight regressionline and the following equation:

where x is equal to the value of the task along the vertical continuum.This interpolation is highly significant, r2 = .97, p < .001.Different interpolations, with the tasks in different orders, were not significant.As for visuospatial working memory (Table 2) we found no significant difference

between the two groups in the two spatial tasks requiring low control, i.e., the pathwayforward and backward tasks. In contrast, individuals with Fragile X showed lower perfor-mance in starting position selection and visuospatial dual task, requiring respectivelymedium-high and high control. Furthermore, scores obtained by typically developingchildren were not affected by increased control (i.e., the control continuum did not simplydescribe increases in task complexity and difficulty). Thus, the greater difficulties childrenwith FXS exhibited in higher control tasks cannot be attributed to the fact that these tasks

difference between groups = − +0 40 0 57. . ,xDow

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tended to produce lower scores. In this case differences between the two groups alsoincrease as the control required by the task increases.

A trend analysis of the gap between groups corresponding to an increase in controlshowed a positive relationship between the two aspects. This relationship could be repre-sented by a positively inclined straight regression line and the following equation:

This interpolation was significant, with r2 = .92 p < .05. Different interpolationswith the tasks differently ordered were not significant. A similar significant trend was alsoobserved when the backward pathway task was excluded.

Further analyses were also run on the standardized z scores, computed on the basisof the distributions for the entire group, which made the scores obtained by the participants inthe different tasks more directly comparable. A 4 (tasks) × 2 (verbal/visuospatial) × 2(groups) MANOVA showed a significant difference between groups, F(1, 28) = 8.91,p < .01, η2 = .241, but, when the performance of the groups was contrasted for each singletask, only the differences of the two groups in the most active verbal and visuospatial taskswere significant. Indeed, the group of individuals with FXS had a significantly lowerperformance than the TD children in selective word recall task, t(28) = 2.531, p < .05, inthe verbal dual task, t(28) = 2.66, p < .05, the starting position selection task, t(28) =3.268, p < .05, and in the visuospatial dual task, t(28) = 2.491, p < .05. In contrast, thedifference between the mean z scores for the other tasks (forward word recall, backwardword recall, pathway forward, pathway backward) was lower and far from significant (forevery comparison p > .05).

DISCUSSION

In our view, the present results offer an important insight in the characteristics ofindividuals with FXS and begin to shed light on the nature of the deficit in the intellectualfunctioning of individuals with intellectual disabilities.

Concerning working memory in FXS, performance in low-control tasks, both verbaland visuospatial, is coherent with mental age, whilst their performance is lower whenmedium-high- and high-control levels are required by the task. In terms of Baddeley’sworking memory model, the results show that the FXS phonological loop and visuospatialsketch-pad functioning are relatively preserved, while central executive functioning isimpaired, given that individuals with FXS attain a lower level of performance thantypically developing children matched for mental age. Results are consistent with otherstudies that showed that individuals with FXS have a performance consistent with theirmental age on tasks requiring low-attentional control in processing simple stimuli, bothverbal and visuospatial (e.g., Cornish et al., 2004; Munir et al., 2000). Moreover, ourresults are in agreement with studies (e.g., Scerif et al., 2004; Wilding et al., 2002) thatfound a central executive deficit in individuals with FXS. Furthermore, in the presentstudy the difference between groups tended to increase in correspondence with increasesin the required degree of control. In this respect, the present results can be specified withreference to a continuum articulated model of working memory (Cornoldi & Vecchi,2003), assuming that the differences between groups can vary in size depending onthe distance along the vertical control continuum. In fact, boys with FXS compared to

difference between the groups = − +0 135 0 674. . .x

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WORKING MEMORY IN FRAGILE X SYNDROME 115

typically developing children displayed an increasing gap in performance moving fromthe most passive to the most active tasks. In the present study the performance differenceswere analyzed with reference to the operations of working memory, but the control issueinvolves the general architecture of mind (Cornoldi & Vecchi) and could also be examinedwith reference to the critical role of controlled attention or to the combined role of mainte-nance and controlled search functions (Unsworth & Engle, 2007).

A large body of preceding evidence has shown that the working memory tasks,which inspired the tasks used in the present study, involve different processes. Therefore,the present results could also be considered with reference to specific processes involvedin the different tasks, but the advantage of an unitary working memory framework, basedeither on Baddeley’s (1986) classical model or on Cornoldi and Vecchi’s (2003) continuityapproach, is that a single main variable seems able to explain the main differences thatcan be observed between individuals with mental retardation and typically developingchildren. Obviously, these results need further support as they could have also beenaffected by other factors. In particular, one may argue that the reliability of low-controlmeasures was low. However, it must be noted that these measures were derived fromclassical verbal and spatial span measures that have already demonstrated, in other contexts,very good discriminative power.

Our results are different from studies in which performance on low-control tasks inindividuals with FXS was lower than in controls matched for mental age, both verbal andvisuospatial (e.g., Cornish et al., 2001; Dykens et al., 1987; Jakala et al., 1997; Munir et al.,2000) or only visuospatial (Shapiro et al., 1995). This could be due to the fact that thestimuli used in these studies were different and more abstract compared with those used inthe present study, as, in order to assess verbal working memory, they used digits (forwardand backward) while we used simple concrete words familiar to the child. Moreover, thestimuli used for the visuospatial task in the present study were also partly different fromthose used in the previous studies. Indeed, the above cited studies required the recall of thelocation of visually presented objects on a white sheet of paper, while in the present studywe required participants to remember the pathway made by a plastic frog. According toseveral authors (e.g., Maes et al., 1994) individuals with FXS recall familiar material moreaccurately than abstract material, and this might explain why we did not find significantdifferences between the groups in these tasks, in contrast with the others authors.

With respect to the distinction between verbal and visuospatial processes, previousstudies (e.g., Jarrold & Baddeley, 1997; Vicari et al., 1995) suggested that specific geneticsyndromes may involve different cognitive profiles. In particular, Down syndrome may becharacterized by a more severe deficit in verbal processes, whereas other syndromes maypresent an opposite pattern, such as is the case of Williams syndrome and velocardiofacialsyndrome (Rourke, 1995). The distinction between verbal and visuospatial components isalso evident from other syndromes, not necessarily associated with intellectual disabilities,such as Turner syndrome (Cornoldi, Marconi, & Vecchi, 2001). Data on individuals withFXS do not appear clear in this respect. The suggestion that individuals with FXS couldhave a specific deficit in visuospatial processes, including the visuospatial sketchpad, wasnot confirmed in the current study. As discussed before our results could be due to the factthat in our task we used very simple stimuli, and recent studies (e.g., Cornish et al., 2004;Munir et al., 2000) found that individuals with FXS have better performance in low-controltasks with simple and familiar items.

The current study is also important in view of the previous study by Lanfranchi et al.(2004), which, using the same battery of tasks, had found a specific verbal deficit in

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individuals with Down syndrome. In fact, the verbal deficit in individuals with Downsyndrome observed in the Lanfranchi et al. (2004) study was not related to a greater sensitivityof the verbal tasks used, but to the specific verbal working memory problems (for a reviewsee, for example, Jarrold & Baddeley, 2001). Thus, current data confirm that differentpopulations of developmental cognitive disabilities can be associated with deficits indifferent working memory components. In Down syndrome there is a verbal workingmemory deficit associated with a control deficit, while fragile X syndrome deficits are notspecific to either verbal or visuospatial tasks, but increase with increasing levels of controlrequired by the task.

At the same time, data support the hypothesis that a general condition of intellectualdisabilities is associated with a specific deficit in the control of working memory. Theseresults offer a further insight into the comprehension of the nature of human intelligence.Indeed, intellectual disabilities, as a condition characterized by a series of cognitive,behavioral, and adaptive symptoms (DSM-IV), are by definition distinguished fromtypical development on the basis of poorer general intellectual functioning. Thus, the indi-viduation of a critical variable underlying the difference between intellectual disabilitiesand typical development may offer an important insight for the comprehension of the criticalfeatures of human intelligence. The present study shows that one critical variable may bethe degree of working memory control. This conclusion further supports the hypothesis ofa relationship between working memory and intelligence, already raised by the piagetianand neopiagetian literature (e.g., Case, 1987) and more recent cognitive research(e.g., Engle, Tuholski, Laughlin, & Conway, 1999), but it also goes a step further, assumingthat the relationship is modulated by the degree of required control. Furthermore, the con-dition of intellectual disabilities is not only defined by cognitive testing but is associatedwith a well-understood genetic etiology. Studying individuals with a genetic syndromeovercomes the risk of circularity present when a difference between groups is found in aspecific cognitive component after having formed the groups on the basis of a cognitiveassessment, which may, potentially, be influenced by the very factor object of study.

Original manuscript received November 21, 2007Revised manuscript accepted April 7, 2008

First published online June 12, 2008

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