ORIGINAL RESEARCH

Spatial Competences in Prader–Willi Syndrome: A Radial ArmMaze Study

Francesca Foti • Deny Menghini • Laura Petrosini •

Giuliana Valerio • Antonino Crino •

Stefano Vicari • Teresa Grimaldi • Laura Mandolesi

Received: 20 December 2010 / Accepted: 20 April 2011 / Published online: 4 May 2011

� Springer Science+Business Media, LLC 2011

Abstract The present study was aimed at investigating

the spatial abilities in Prader–Willi syndrome (PWS) by

using the Radial Arm Maze (RAM) task. We trained PWS

individuals with the deletion subtype in two different RAM

paradigms that tapped different aspects of spatial memory.

To evaluate the extent of spatial deficit in PWS individuals,

it seemed interesting to compare their performances with

those of individuals with Williams syndrome (WS) in

which deficits in spatial abilities have been well described.

The two syndromic groups were compared to typically

developing (TD) individuals mental-age and gender mat-

ched. The findings evidenced the impairment of PWS

individuals in solving the RAM task with variable severity

depending on the paradigm requests. Since the RAM is a

task that allows the acquisition of spatial competences

through the movement, we advance that the spatial deficits

observed in PWS individuals may be related to the mal-

functioning of spatial and motor integrative processing.

Keywords Spatial ability � Spatial working memory �Procedural components � Genetic syndromes �Cognitive behavior

Introduction

Prader–Willi syndrome (PWS) is a genetical disorder

caused by either the paternal deletion within 15q11–q13

(70–75% of cases), or the maternal uniparental disomy of

chromosome 15 (UPD) (20–25%), or a defect in the

imprinting centre (2%) with an incidence rate at birth at

about 1:10,000–1:25,000 (Woodcock et al. 2009).

PWS is characterized by hyperphagia, early-onset and

morbid obesity, hypogonadism, hypotonia and short stature.

Furthermore, inappropriate behaviors, as social withdrawal,

perseverative behaviors, mental rigidity, impulsiveness,

explosive outbursts, etc. are described in PWS individuals

(Ho and Dimitropoulos 2010). These maladaptive behaviors

have been related to a dysfunctioning of the elementary

frontal cognitive processes (Jauregi et al. 2007). This

hypothesis was confirmed by a recent voxel based MRI

study that showed reduced gray matter volume in the orbito-

frontal cortex (Ogura et al. 2010) retained to play a crucial

role in several functions and in compulsive behavior in

particular (Kim and Lee 2002).

PWS cognitive profile has not been thoroughly investi-

gated as it occurred in other genetic syndromes (Williams,

Down, fragile X syndromes). Neuropsychological stud-

ies reported that PWS individuals perform better on

Edited by Petrus de Vries and Pierre Roubertoux.

F. Foti � L. Petrosini � L. Mandolesi (&)

IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 65,

00143 Rome, Italy

e-mail: laura.mandolesi@uniparthenope.it

F. Foti � L. Petrosini

Department of Psychology, University of Rome ‘‘Sapienza’’,

Rome, Italy

D. Menghini � S. Vicari

Child Neuropsychiatry Unit, Neuroscience Department,

‘‘Children’s Hospital Bambino Gesu’’, Rome, Italy

G. Valerio � L. Mandolesi

School of Movement Sciences (DiSIST), University of Naples

‘‘Parthenope’’, Via Medina 40, 80133 Naples, Italy

A. Crino � T. Grimaldi

Pediatric and Autoimmune Endocrine Disease Unit, ‘‘Children’s

Hospital Bambino Gesu’’, Palidoro, Rome, Italy

123

Behav Genet (2011) 41:445–456

DOI 10.1007/s10519-011-9471-4

visuo-spatial and simultaneous processing tasks than on

verbal and sequential ones (Dykens et al. 1992). Their short-

term memory is more severely affected than long-term

memory (Conners et al. 2000). Deficits have been observed

in fine motor tasks (Levine and Wharton 1993), auditory

tasks (Curfs et al. 1991), executive functions (Gross-Tsur

et al. 2001; Walley and Donaldson 2005; Jauregi et al.

2007) and attentive functions (Relkovic et al. 2010;

Woodcock et al. 2010). PWS individuals usually exhibit

mild-to-moderate learning disabilities (Whittington et al.

2004). However, not all PWS patients conform to the same

profile, and the differences have been correlated with the

different genotypes (Dykens 2002), although the precise

role of genes mapped in determining specific PWS features

is still under debate (Titomanlio et al. 2006). Namely, if we

considered intelligence measures as evaluated by Wechsler

intelligence scales, individuals with the deletion subtype

have strengths in the performance subtests, while subjects

with the UPD subtype have strengths in the verbal subtests

(Curfs et al. 1991; Whittington et al. 2004). Moreover, some

PWS individuals with deletion (but not individuals with the

UPD subtype) show good performance on jigsaw puzzles, a

task linked to visuo-spatial processing (Dykens 2002;

Verdine et al. 2008). This observation fits with the good

capacities of spatial learning and localizatory memory

described in an animal model deficient for Necdin, gene

strongly candidate in PWS ethiology (Muscatelli et al.

2000). However, a recent clinical study reported a marked

impairment of visuo-spatial abilities in PWS participants

with deletion when required to judge the locations of simple

visual shapes, suggesting thus that visuo-spatial abilities

would not be strength in PWS individuals with deletion

(Woodcock et al. 2009).

Taking into account these controversial evidences, it

seemed interesting to characterize the visuo-spatial abilities

of PWS individuals with deletion to evaluate the extent of

their eventual spatial deficits. To this aim, we tested the

individuals’ performances by using the Radial Arm Maze

(RAM) that allows analyzing through movement most

facets of the spatial function, as the spatial working

memory and the declarative memory (Jarrard 1993; Man-

dolesi et al. 2001), as well as the searching strategies put

into action in executing the spatial task (Overman et al.

1996; Mandolesi et al. 2009a). Namely, in the spatial tasks

as the RAM, to encode spatial relationships of an envi-

ronment (declarative spatial knowledge), it is develop-

mentally and temporally necessary to learn ‘‘how’’ to

move in that environment (procedural spatial knowledge)

(Fenton and Bures 1993; Foti et al. 2011). Thus, to profi-

ciently solve RAM task procedural competences, working

memory functions as well as mapping abilities are equally

necessary (O’Keefe and Nadel 1978; Overman et al. 1996;

Mandolesi et al. 2009a).

In the present research we compared the performances

of PWS individuals with deletion with those of individuals

affected by Williams syndrome (WS) that are retained to

have a specific impairment of visuo-spatial abilities (Vicari

et al. 2006) and in which behavior in the RAM has been

previously described (Mandolesi et al. 2009b) in order to

evaluate whether spatial deficits found in PWS individuals

could be of similar extent to the spatial deficits described in

WS individuals.

Methods

Participants

We examined the performances in the free-choice RAM

paradigm of 12 right handed individuals with PWS with the

deletion subtype (6 males and 6 females) with a mean

chronological age (CA) of 17.04 years (SE ±1.5; age

range: 8–30 years), a mean mental age (MA) of 6.06 years

(SE ±0.5; age range: 4–9 years). Twelve right handed

individuals with WS, MA matched with PWS (MA:

6.06 years, SE ±0.3; age range: 5–8 years; CA:

16.02 years, SE ±1.5; age range: 9–26 years) formed the

syndromic control group. Fifteen right-handed typically

developing (TD) children (7 males and 8 females), MA

matched with both PWS group and WS group (MA:

6.05 years; SE ±0.4; CA: 6.06 years; SE ±0.5), formed

the control group.

The day after the third session of the free-choice para-

digm, a subgroup of PWS and WS participants was tested

in a forced-choice RAM paradigm. The reason for this

‘‘sample mortality’’ was due to the fact that some partici-

pants either were not present on one of the two days of

forced-choice RAM paradigm or refused to perform the

game again. Namely, 10 PWS individuals (5 males and 5

females), with a mean CA of 17.06 years (SE ±2.9; age

range: 9–30 years) and a mean MA of 6.08 years (SE

±0.5; age range: 4–9 years) and 10 WS individuals (5

males and 5 females; CA: 16.06 years; SE ±1.6; age range:

11–26 years; MA: 6.07 years; SE ±0.3; age range:

5–8 years) were submitted to this protocol. Thirteen TD

children (6 males and 7 females) who matched the PWS

and WS participants for MA (MA: 6.09 years; SE ±0.4;

CA: 6.09 years; SE ±0.5) formed the control group.

All pathological participants were part of a larger pool

of individuals attending the Children’s Hospital Bambino

Gesu for clinical and rehabilitative follow up and were

selected for the study if having a mental age level of

around 6 years. In all PWS and WS participants, the clin-

ical diagnosis was confirmed by genetic investigation

(FISH), which showed the paternal deletion on chromo-

some band 15q11–q13 (in PWS) and the deletion on

446 Behav Genet (2011) 41:445–456

123

chromosome band 7q11.23 (in WS). All PWS participants

had been receiving pharmacological treatment GH therapy

for at least 3 years and were in euthyroidism. All syn-

dromic participants lived with their own families.

All TD children attended a public elementary school in

Central Italy and their recruitment was random.

None of the participants had had previous experience

with RAM. Evaluations were made after informed consent

was obtained from all participants and their families and

the study had been approved by the local ethics committee.

All participants had normal or corrected vision.

Behavioral assessment

A neuropsychological battery was administered to each

PWS, WS and TD participant in three separate sessions

over three consecutive days. In all groups, MA was eval-

uated with the L-M form of the Italian version of the

Stanford-Binet Intelligence Scale (Bozzo and Mansueto

Zecca 1993). Furthermore, in all groups the following

cognitive domains were explored: linguistic abilities:

lexical production (Boston Naming Test—BNT; Riva et al.

2000) and lexical comprehension (Peabody Picture

Vocabulary Test—PPVT; Stella et al. 2000); visuo-spatial

short-term memory abilities (visuo-spatial span—VSS and

visual-object span—VOS; Vicari 2007); visual perceptive

abilities: (Visual Perception Test—VPT subtests 2 and 4;

Hammill et al. 1994); visuo-motor abilities: Developmental

Test of Visual-motor Integration (VMI; Beery 2000).

RAM apparatus

It consisted of a round central platform (1 m in diameter)

with eight arms (50 cm wide 9 6 m long) radiating like

the spokes of a wheel (Fig. 1). To force the subjects to

return to the centre of the starting platform before entering

another arm and thus to prevent them from ‘‘cutting cor-

ners’’, the sides of each arm were marked off by white and

red ribbons forming a sort of constraining barrier. At the

end of each arm, there was an orange plastic bucket (18 cm

wide 9 28 cm high) containing the reward (a little colored

ball). The RAM, located outdoors in a large garden, was

surrounded by extra-maze cues (trees, swings, benches,

etc.) held in constant spatial relations throughout the

experiment. Only during the experimental testing the sub-

jects could see the maze or have physical access to it. To

increase the motivation to pick up the rewards, at the end of

each trial the subject received a reward (a coin) in

exchange for all the colored balls found in the buckets.

To retrieve the rewards, the subject could put algorith-

mic strategies into action by choosing to visit a specific

sequence of arms, for example by entering adjacent,

opposite or alternate arms, or beginning a run always from

the same arm, etc. Additionally, the subject could make

reference to environmental stimuli located close to (intra-

maze cues) or far from (extra-maze cues) the rewarded site.

Finally, the subject could build an internal representation

of the environment (cognitive spatial map) to explore the

maze (Jarrard 1993).

We administered two RAM paradigms, the free-choice

paradigm that allowed analyzing the spatial mnesic com-

ponents and explorative strategies and the forced-choice

paradigm that permitted mainly evaluating the short

memory capabilities, distinguished mnesic from procedural

components.

Free-choice paradigm

Each subject was allowed to freely explore the eight arms

to retrieve the rewards. A trial ended when all eight

rewards had been collected, 20 choices had been made, or

15 min had elapsed from the start of the task. Since the

buckets were never rewarded twice, the optimal perfor-

mance consisted of visiting each bucket only once. An

error was made when the subject re-entered an arm already

visited during the same trial. At the end of the trial, the

subject waited for 1 h (inter-trial interval), before being re-

tested in the maze. Each subject performed three trials a

day for three consecutive days. Since the three daily trials

constituted a session, each subject made three sessions for a

total of nine trials.

At the beginning of the first test day, to explain the task

to each subject the experimenter used the same simple

verbal instructions supporting them with hand gestures,

facial expressions and intonation. Moreover, to be sure to

get participants’ attention the experimenter kept eye con-

tact with them. The verbal instructions were: ‘‘The game is

to find some little colored balls. Do you see the colored

buckets at the end of each alley? You have to reach a

bucket, take the little ball inside, and then go back to the

centre, where the platform is, until you have collected all

the balls. Be careful to reach the buckets always staying

inside the maze. Go and have fun!’’. No other instructions

or verbal encouragement were provided during the testing.

To make sure the participants understood the instructions,

the experimenter asked one participant to explain what he/

she had to do. The subjects’ behaviors during the sessions

were videotaped and recorded manually.

Behavioral parameters To assess the subject’s perfor-

mance we evaluated the total time (in s) spent to complete

the task and the arm time (in s), calculated as total time

divided by the number of visited arms, including those

consisting in errors. Since not all subjects succeeded in

collecting the eight rewards in the allotted time (15 min) or

in the 20 pre-established number of entries, we introduced

Behav Genet (2011) 41:445–456 447

123

the frequency of successes, calculated as the number of

subjects belonging to each group that completed the task by

collecting the eight rewards. We considered also the

latency (in s) to visit the first arm; the percentage of correct

visits, calculated as the percentage of correctly visited arms

divided by the number of entries; the errors, considered as

re-entries into already visited arms; the spatial span, cal-

culated as the longest sequence of correctly visited arms;

the percentage of angled turns, calculated as the number of

a given angle (45�, 90�, 135�, 180�, or 360�) the subject

made in each trial divided by the number of angles

made 9 100; the perseverations, calculated as the per-

centage of consecutive entries into the same arm or the re-

entries into a fixed sequence of arms, divided by the

number of arms visited; the spatial acuity index, calculated

as the ratio between the number of times an allocentric

strategy was used out of the nine trials (Janis et al. 1998;

Lehmann et al. 2002, 2003).

Forced-choice paradigm

In this paradigm, each trial consisted of two phases. In the

first phase, only four arms (for example, arms 1, 3, 4, 7)

were reinforced and the remaining four arms were closed

by a little chair at the proximal end of each arm. Subjects

were allowed to explore the four open arms. Afterwards,

they were guided out of the maze and were taken to a place

where they could no longer see the maze and where they

spoke with the experimenter for 120 s before starting the

second phase. In the second phase, subjects had free access

to all arms, but only the four previously closed arms were

reinforced. Regular search patterns were discouraged by

the irregularity and variation of the rewarded arms distri-

bution. Thus, this paradigm emphasized mnesic require-

ments rather than procedural strategies of the task.

The subjects performed three trials a day for two suc-

cessive days, with an inter-trial interval of at least 1 h. In

each of the three daily trials, a different configuration of

arms closed was provided to avoid any fixed search pattern.

At the beginning of the first trial, the experimenter

explained the task to each subject by using the same simple

verbal instructions (‘‘You have to pick up the little balls

inside the buckets by entering only the alleys without

chairs. Go and have fun!’’). The verbal instructions after

the 120 s-interval were: ‘‘To win the little toy as you did

previously, now you have to finish the game. As you can

see, there are no more chairs. Remember, you may find the

little balls in the buckets of the alleys that were closed

before by the chairs! Do a good job and come back a

winner!’’.

The first session was considered as a session to get used

to the new testing since most subjects did not end the trial,

asked explanations to experimenter, stopped for a while

watching around and so on. So, only the results of second

session (trials 4–6) were statistically analyzed. At the end

of the task, all PWS individuals were asked to drawing the

radial maze but all of them, maybe for their negative

behavior, were incapable of drawing it, at odds with WS

subjects that from 6 years of MA onwards were able to

represent the setting in an organized manner (Mandolesi

et al. 2009b). For this reason, in the present research rep-

resentative graphic abilities were not investigated.

Fig. 1 View of the eight-arm

radial maze. Note the plastic

buckets containing the rewards

at the end of the arms

448 Behav Genet (2011) 41:445–456

123

Behavioral parameters The parameters taken into

account were the working memory errors, considered as re-

entries into already visited arms. This parameter was

broken down further into two error subtypes: across-phase

errors, defined as entries into an arm that had been entered

during the first phase of the same trial; within-phase errors,

defined as re-entries into an arm already visited in the same

phase. Moreover, we considered the percentage of 45�angled turns in the second phase, calculated as already

described in ‘‘Behavioural parameters’’ of the ‘‘Free-

choice paradigm’’.

Statistical analysis

Metric unit results were first tested for homoscedasticity of

variance. The data obtained from the different parameters

presented as means ± SEM were analyzed by using one-

way or two-way analyses of variance (ANOVAs) with

repeated measures followed by post hoc multiple com-

parisons (Tukey’s test). The dichotomous variables were

analyzed by Chi square test. Data correlation was also

tested by means of coefficient Pearson’s r.

Results

Neuropsychological assessment

The statistical comparisons of the results obtained by

experimental groups are shown in Table 1. As expected, in

the linguistic abilities PWS and WS groups obtained worse

scores than TD children in VSS task. A similar pattern was

found in VPT2 and in VMI.

Free-choice paradigm

The first day of the testing, PWS individuals showed

negative emotional behavior such as wariness for the

experimenter and for the new game. For this reason, the

experimenter spent some time talking long with every

participant before starting the task without providing no

further information about the task. In contrast, the behavior

of WS individuals was extraordinarily friendly and they

seemed very interested to perform the game. Features

shared by the two syndromic groups were slowness of the

movements, requests for further instructions during the

task, and ease distractibility. Because of these character-

istics the PWS and WS individuals took about 60 s more

than TD subjects to explore the maze (Fig. 2a). A two-way

ANOVA (group 9 session) revealed a significant group

effect (F2,36 = 11.56; P \ 0.0005; g2 = 0.39), while ses-

sion effect (F2,72 = 1.89; P n.s.) and interaction

(F4,72 = 0.6; P n.s.) were not significant. Post hoc Ta

ble

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Behav Genet (2011) 41:445–456 449

123

comparisons on group effect revealed significant differ-

ences between pathological groups versus TD subjects

(PWS vs. WS: P n.s.; PWS vs. TD: P \ 0.001; WS vs. TD:

P \ 0.005). Similar pattern was found in the arm time

parameter. In fact, PWS and WS individuals took about

16 s to explore an arm (Fig. 2b), while TD participants

about 9 s. A two-way ANOVA (group 9 session) revealed

a significant group effect (F2,36 = 8.35; P \ 0.005;

g2 = 0.31), while the session effect (F2,72 = 0.42; P n.s.)

and interaction (F4,72 = 0.6; P n.s.) were not significant.

Post hoc comparisons on group effect revealed significant

differences between pathological groups versus TD sub-

jects (PWS vs. WS: P n.s.; PWS vs. TD: P \ 0.005; WS

vs. TD: P \ 0.05).

The latency times in visiting the first arm were similar in

all groups, as revealed by a two-way ANOVA

(group 9 session) (group effect: F2,36 = 1.44; P n.s.; ses-

sion effect: F2,72 = 0.28; P n.s.; interaction: F4,72 = 2.3;

P n.s.). In fact, all groups went to the first arm in about 2 s,

indicating they were similarly motivated in performing the

task.

Only a limited number of PWS and WS individuals

succeeded in collecting the eight rewards. In particular,

while all TD children successfully completed the task in

any session, only 3 PWS and 5 WS participants in the first

session (Chi square = 10.78, df = 2, P \ 0.005), 3 PWS

and 4 WS participants in the second session (Chi

square = 12.09, df = 2, P \ 0.005) and 5 PWS and 4 WS

participants in the third session (Chi square = 9.25,

df = 2, P \ 0.01) correctly completed the task.

As shown in Fig. 2c, PWS individuals performed the

task making a significantly lower number of errors in

comparison to WS individuals (post hoc comparison:

P \ 0.0005), while their number of errors did not differ

from those of TD children (post hoc comparison: P n.s.). A

two-way ANOVA (group 9 session) revealed significant

group (F2,36 = 17.9; P \ 0.0001; g2 = 0.49) and session

(F2,72 = 4.83; P \ 0.05; g2 = 0.11) effects, while the

interaction was not significant (F4,72 = 0.2; P n.s.). Only

TD individuals significantly decreased the number of

errors, as the sessions went by (one-way ANOVA:

F2,28 = 4.89; P \ 0.05; g2 = 0.26).

The spatial span (the longest sequence of correctly

visited arms) provided information on working memory

abilities and/or procedural competencies, since high spatial

span values could be obtained exploiting working memory

and mapping abilities or efficient explorative strategies. A

two-way ANOVA (group 9 session) revealed significant

group (F2,36 = 21.31; P \ 0.0005; g2 = 0.54) and session

(F2,72 = 4.08; P \ 0.05; g2 = 0.10) effects, while the

interaction was not significant (F4,72 = 0.36; P n.s.)

(Fig. 2d). Post hoc comparisons on group effect revealed

significant differences among groups (PWS vs. WS: P \0.01; PWS vs. TD: P \ 0.05; WS vs. TD: P \ 0.0005).

Fig. 2 Performance of the

PWS, WS and TD individuals

on the motor and spatial

parameters of the free-choice

paradigm. In this and in Figs. 3

and 4 vertical bars indicate SEM

450 Behav Genet (2011) 41:445–456

123

Once again, only TD children increased the values of

spatial span, as the sessions went by (one-way ANOVA:

F2,28 = 4.93; P \ 0.05; g2 = 0.26).

In both PWS and WS groups, the correlations between

RAM performances (expressed as the mean spatial span)

and visuo-spatial abilities (expressed as the mean span on

VSS task) were considered. In each group the correlation

(Pearson’s coefficient) between measures considered was

not significant (PWS: RAM spatial span versus VSS span:

r = -0.02, P n.s.; WS: RAM spatial span versus VSS

span: r = -0.10, P n.s.).

The angles performed in visiting the arms were specif-

ically linked to the procedural strategies put into action in

exploring the maze. The distribution of the various angled

turns (45�, 90�, 135�, 180� and 360� angles) performed by

all groups is represented in Fig. 3a. The individuals of all

groups made primarily 45� angles, indicating a marked

preference to enter adjacent arms. Only WS individuals

made 90� and 135� angle percentages significantly differ-

ent than PWS and TD subjects. A two-way ANOVA

(group 9 angle) did not reveal significant group effect

(F2,36 = 1.62; P n.s.), while angle effect (F4,144 = 342.69;

P \ 0.0001; g2 = 0.90) and the interaction were signifi-

cant (F8,144 = 14.46; P \ 0.0001; g2 = 0.44).

Given the high percentage of 45� angles displayed by all

groups, their distribution throughout the sessions was

analyzed in detail (Fig. 3b). A two-way ANOVA (group 9

session) revealed a significant group effect (F2,36 = 14.62;

P \ 0.0001; g2 = 0.44). The session effect was not sig-

nificant (F2,72 = 0.37; P n.s.), while the interaction was

significant (F4,72 = 3.34; P \ 0.05; g2 = 0.15).

PWS individuals made a significantly higher percentage

of 45� angles than WS individuals in all sessions (post hoc

comparisons: always at least P \ 0.01) while in compari-

son to TD children, they exhibited lower percentages only

in the second session (P \ 0.01).

We considered the 45� angle span, that is the average

string of adjacent arms consecutively entered, as a further

measure of the use of a chaining strategy (Fig. 3c). A two-

way ANOVA (group 9 session) on 45� angle span

revealed a significant group effect (F2,36 = 16.72; P \0.0001; g2 = 0.48), while session effect (F2,72 = 0.17;

Fig. 3 Performance of PWS,

WS and TD individuals on the

procedural parameters of the

free-choice paradigm

Behav Genet (2011) 41:445–456 451

123

P = n.s.) and interaction (F4,72 = 0.98; P n.s.) were not

significant. In comparison to TD children, PWS and WS

individuals made significantly shorter mean 45� angle span

(PWS = 5.9 ± 0.35; WS = 4.4 ± 0.47; TD = 7.4 ±

0.32; post hoc comparisons: PWS vs. WS: P \ 0.05; PWS

vs. TD: P \ 0.05; WS vs. TD: P \ 0.0005).

The perseverations that is the consecutive entries into

the same arm or into a fixed sequence of arms, were present

almost exclusively in PWS and WS individuals (Fig. 3d).

Although the occurrence of perseverations was low in both

groups, WS individuals made a major number (post hoc

comparison: PWS vs. WS: P \ 0.05). A two-way ANOVA

(group 9 session) revealed a significant group effect

(F2,36 = 13.61; P \ 0.00005; g2 = 0.43). Neither the ses-

sion effect (F2,72 = 2.48; P n.s.) nor the interaction

(F4,72 = 0.96; P n.s.) were significant.

The spatial acuity index assesses whether the subjects

use allocentric strategies to solve the task and if they are

sensitive to the environmental cues. As shown in Fig. 3e,

only PWS and TD participants used an allocentric strategy.

One-way ANOVA revealed a significant group effect

(F2,36 = 4.62; P \ 0.05; g2 = 0.20), due to the signifi-

cantly lower value in WS individuals in comparison to

PWS and TD participants (post hoc comparisons: PWS vs.

WS: P \ 0.05; PWS vs. TD: P n.s.; WS vs. TD: P \ 0.05).

Forced-choice paradigm

When facing the first phase, PWS and WS individuals

completed the task, on average, making 0.5 ± 0.18 errors

and 1 ± 0.32 errors respectively, while TD children’ per-

formance was almost error-free (one-way ANOVA:

F2,30 = 5.22; P \ 0.05; g2 = 0.26) (Fig. 4a). Post hoc

comparisons between groups revealed significant effect

only when WS and TD subjects were compared (P \ 0.01).

In the second phase, PWS subjects made on average

3.6 ± 0.24 errors, a value that did not differ from TD

(2.4 ± 0.29) individuals’ errors (one-way ANOVA:

F2,30 = 5.17; P \ 0.01; g2 = 0.26; post hoc comparisons:

PWS vs. WS, P n.s.; PWS vs. TD, P n.s.; WS vs. TD,

P \ 0.05) (Fig. 4a).

An additional analysis on the mnesic errors revealed that

all groups made more across-phase errors (entries into an

arm that had been visited during the first phase) than

within-phase errors (re-entries into an arm previously vis-

ited in the same phase) (Fig. 4a). A two-way ANOVA

(group 9 type of error) revealed significant group

(F2,30 = 5.84; P \ 0.001; g2 = 0.28) and type of error

effects (F1,30 = 510.28; P \ 0.0001; g2 = 0.94). Also the

interaction was significant (F2,30 = 6.93; P \ 0.005;

g2 = 0.31). While all groups made a similar number of

within-phase errors, PWS and WS individuals performed

significantly higher number of across-phase errors in

comparison to TD children (PWS vs. WS, P n.s.; PWS vs.

TD, P \ 0.001; WS vs. TD, P \ 0.0005).

In order to assess whether the high number of errors

performed by the PWS participants in the second task

phase could be related to the inappropriate use of algo-

rithmic strategies or short-term memory deficits, we ana-

lyzed in details the 45� angle distribution. In fact,

performing 45� angles was the main strategy performed by

all subjects in the free-choice paradigm.

In Fig. 4b is shown that in the second phase of the task

all participants performed a high percentage of 45� angles,

although with significant differences among them. Namely,

especially TD individuals used this strategy to visit correct

arms. On the contrary, both syndromic groups performed

45� angles to indistinctly visit correct and incorrect arms. A

two-way ANOVA (group 9 kind of angle) did not reveal

Fig. 4 Performance of PWS, WS and TD individuals on mnesic and

procedural parameters of forced-choice paradigm in the first and

second phase of the test. The asterisks inside the graphs indicate the

significance level of post hoc comparisons among groups,

*P \ 0.001; **P \ 0.0005; ***P \ 0.00005

452 Behav Genet (2011) 41:445–456

123

significant group effect (F2,30 = 2.34; P n.s.), while angle

effect was significant (F1,30 = 21.77; P \ 0.0001;

g2 = 0.42). The interaction was also significant

(F1,30 = 6.22; P \ 0.005; g2 = 0.29).

Discussion

By comparing their free-choice RAM performances with

those of TD children matched for sex and MA, PWS

individuals appeared impaired in some parameters, while

displaying similar performances in others. Namely, in

selecting the first arm PWS individuals’ latencies did not

differ from those of TD children, demonstrating that both

groups were similarly motivated in performing RAM task.

Furthermore, PWS and TD individuals exhibited similar

numbers of errors, although only TD children decreased the

errors throughout the task. Even the percentages of entries

in consecutive arms (45� angles) and the spatial acuity

index were similar between groups. Conversely, PWS

individuals performed worse than TD children on the

parameters more specifically linked to spatial working or

long-term memory and to complex explorative strategies,

as the chaining strategy. In fact, PWS participants exhib-

ited lower values of spatial span and reduced string of

adjacent arms consecutively entered. As a notation, we

underline, at odds with TD children, PWS individuals

exhibited perseverative tendencies that revealed the pres-

ence of explorative deficits and severe problems in initia-

tion/perseveration and cognitive planning. Of course, the

presence of perseverations could be responsible for longer

total time and arm time, increased number of errors and

shorter spatial span the PWS individuals exhibited. Note

that low digit span scores have been recently reported in a

large cohort of adults with PWS (Copet et al. 2010), con-

firming the impairment in short-term and working memory

previously reported (Cassidy et al. 1997; Jauregi et al.

2007).

In the forced-choice paradigm, when the task was more

difficult, as in the second phase characterized by all the

eight arms opened, PWS individuals performed a signifi-

cantly higher number of across-phase working memory

errors in comparison to TD children. As a notation, we

underline that this paradigm was rather difficult even for

TD children, as indicated by their less than perfect per-

formances. In fact, when the mnesic load was increased, as

in the second phase, the TD children did not succeed in

making error-free performances, as they did in the first

phase. The difficulties observed in TD individuals might be

related to the limited memory span in the ages considered.

In fact, memory span increases with age: while at 5 years

of age, the short-term memory span is about 3, at 12 years

of age the span becomes 6 or 7 (Hulme and Mackenzie

1992). These difficulties might explain why both PWS and

TD groups continued to put into action mainly an algo-

rithmic strategy (45� angles) in the forced-choice para-

digm, although the high percentage of 45� angles was

qualitatively different between groups. Namely, TD indi-

viduals used the algorithmic strategy of 45� angles to make

mainly right visits, while PWS participants indistinctly

used it to perform right and wrong visits.

Summing up, by testing spatial competences in PWS

individuals by means of RAM, we detected the presence of

spatial deficits, rather unexpectedly considering the visuo-

spatial domain was considered a strength point of this

pathology (Curfs et al. 1991; Dykens et al. 1992; Dykens

2002; Verdine et al. 2008). Evidently, the spatial perfor-

mances could be differently affected according to the kind

of spatial task PWS individuals were tested on. In fact, the

indication that PWS individuals perform better on visuo-

spatial and simultaneous processing tasks than on verbal

and sequential ones has been advanced by testing the

perceptual organization and visuo-motor integration by

VMI, Object Assembly and Triangles tasks (Dykens 2002).

The behavioral spatial tasks, such as RAM, mainly ana-

lyzes spatial mnesic and procedural components in a situ-

ation in which the level of mental representation of spatial

setting is reduced and allows to facet spatial function.

We wondered whether spatial deficits found in PWS

individuals could be of similar extent to the spatial deficits

described in WS individuals in whom deficits in the

acquisition of spatial competences (Mandolesi et al. 2009b)

and in the visuo-spatial memory processes (Vicari et al.

2006) have been repeatedly described (Atkinson et al.

2003). In fact, at variance with PWS, the cognitive profile

(aspects of language relatively proficient and visuo-spatial

abilities, counting, planning and implicit learning severely

impaired) and neuro-pathological abnormalities (impair-

ment of dorsal cortical stream and volumetric reduction of

the posterior portions of the corpus callosum connecting

the parietal lobes) have been well described in WS

(Atkinson et al. 2006; Tomaiuolo et al. 2002). Thus, it

seemed interesting to compare performances exhibited by

WS and PWS individuals on exactly the same spatial task.

In the free-choice RAM paradigm, PWS individuals dis-

played lower number of errors, longer values of spatial

span, higher percentages of 45� angle, lower incidence of

perseverations, higher spatial acuity index in comparison to

WS subjects. Thus, in all parameters of free-choice RAM

paradigm PWS participants showed significantly less

severe spatial (either mnesic and procedural) deficits than

WS individuals.

However, when the task required to be solved basing

only on spatial working memory components as it occurred

in forced-choice RAM paradigm, the performances of both

syndromic groups became not significantly different

Behav Genet (2011) 41:445–456 453

123

indicating an impairment of spatial memory in both path-

ological conditions. Furthermore, also the correlations

between the performances of PWS and WS individuals in

the RAM task with the respective performances obtained in

VSS evidenced no significant difference in both groups. As

a whole, such findings allow characterizing the spatial

deficits of both syndromic groups as related to specific

impairment in visuo-spatial memory, regardless the spatial

tasks they performed. Furthermore, the minor severity of

the spatial deficit observed in PWS in comparison to WS

individuals could be linked to the concomitant procedural

impairment displayed by WS individuals, as indicated by

their reduced use of the most efficient exploration strategy,

as visiting adjacent arms by performing 45� angles, in the

free-choice paradigm. It is necessary to emphasize that the

RAM is a task that requires the acquisition of spatial

competences through the movement, since the subject must

move in the environment to solve the task. Thus, the

impairment found in PWS individuals in executing the

RAM task could be linked to either a deficit of the spatial

competences or a deficit of motor competences or a deficit

that was the product of both of them. A specific deficit of

the acquisition of spatial competences is difficult to rec-

oncile with the indication that PWS individuals are rather

competent in solving other spatial tasks, as for example the

jigsaw puzzles that require efficient visuo-spatial process-

ing (Verdine et al. 2008). Similarly, the presence of a mere

motor deficit does not fit with the observation that PWS

individuals we tested on the RAM showed no obvious

motor deficits but a slowed down execution of the task that

however does not prevent them to perform the task. Con-

versely, the spatial deficits of PWS individuals might be

related to a defective interaction of spatial and motor

domains and more specifically to how the motor system

modules and affects the acquisition of spatial competen-

cies. In fact, considering spatial abilities disconnected from

motor processes appears an oversimplification since the

knowledge of environment is largely acquired through the

ability to move in it (Lehnung et al. 2003; Etienne and

Jeffery 2004). Several studies have demonstrated that

perception, action and cognition are closely linked to the

processing of spatial information (Matelli and Luppino

2001; Buneo and Andersen 2006). For example, neuroim-

aging studies on healthy humans have reported that pos-

terior parietal cortex is activated in spatial attention and in

movement tasks (Culham et al. 2003; Ikkai and Curtis

2008). The defective interaction between perception and

action processes would also explain the deficit in tasks

testing perception (VPT subtests 2) and visual-motor

integration (VMI) and the specific reduced ability visuo-

perceptual organization in PWS individuals (Jauregi et al.

2007; Woodcock et al. 2009). This interpretation is con-

sistent also with the deficits of PWS individuals in spatial

organization of relations between numbers (Bertella et al.

2005; Semenza et al. 2008) and in executive processes

(Gross-Tsur et al. 2001; Walley and Donaldson 2005;

Jauregi et al. 2007), functions related to frontal and parietal

association areas.

Only very few studies have investigated brain abnor-

malities caused by the chromosomal defect in PWS.

Hayashi et al. (1992) reported neuro-pathological anoma-

lies in the cerebellar structures. By using three-dimensional

MRI, Miller et al. (2007) evidenced a decreased volume of

brain tissue in the parietal-occipital lobe. Very recently,

Ogura and collaborators have evidenced reduced gray-

matter volume including the orbito-frontal cortex, caudate

nucleus, inferior temporal gyrus, precentral gyrus, supple-

mentary motor area, postcentral gyrus, and cerebellum

(Ogura et al. 2010). Neuro-anatomical abnormalities of

fronto-parietal network were also found in individuals with

paternal deletion PWS performing a task switching

(Woodcock et al. 2010). It is thus possible to suggest that

these neuro-anatomical abnormalities may be the structural

basis of the impaired spatial functions of PWS subjects

here described. Furthermore, the current findings can be

nicely correlated with the results obtained in the experi-

mental research. In fact, by using an animal model of PWS

with a defect in the imprinting centre, Relkovic and

co-workers reported impaired abilities in a five-choice

serial reaction time task related to frontal abnormalities

(Relkovic et al. 2010).

Although further confirmation is needed, findings of

spatial deficits observed by PWS individuals related to the

relation between spatial and motor competences might

have important rehabilitative implications. Understanding

how individuals with genetic syndromes process spatial

information allows designing intervention strategies that

might make patients more autonomous. Being able to

explore the environment has many positive aspects: it

allows to interact with the elements within it, stimulating

their knowledge, it allows to go from one location to

another, increasing the development of orientative abilities

as well as the motor activity, both functions that may be

related to improved cognitive functions. In addition,

enhanced ability to move around permits interacting

actively not only with environmental stimuli but also with

the other individuals, increasing thus socialization and

communication functions impaired in the presence of PWS.

One possible limitation of the present study is the

mental age matching criteria for selecting participants

(around 6 years old). Indeed, it could be that participants

with WS or PWD were not fully representative of their own

group since their mean cognitive level could be situated in

the higher level of their group. However, because of the

typology of the experimental procedure adopted in the

study we need a good compliance in executing the tasks

454 Behav Genet (2011) 41:445–456

123

and to select participants with a cognitive maturation of at

least 6 years.

This notwithstanding, the results of present research

indicating a deficit in PWS subjects when spatial compe-

tencies are acquired through active exploration of the

environment suggest a malfunctioning of spatial and motor

integrative processing.

Acknowledgments We would like to thank S. Spera for her cour-

teous help in organizing children’s schedule and E. Orlandi for his

kind help in testing some children. We would like also to thank the

children with Prader–Willi and Williams syndromes and their parents

for making this study possible. This work was supported by MIUR

grants to LP.

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