Dissociation of Cross-Sectional Trajectories for Verbal and Visuo-Spatial Working Memory Development in Rubinstein-Taybi Syndrome

Abstract

Working memory (WM) impairments might amplify behavioural difference in genetic syndromes. Murine models of Rubinstein-Taybi syndrome (RTS) evidence memory impairments but there is limited research on memory in RTS. Individuals with RTS and typically developing children completed WM tasks, with participants with RTS completing an IQ assessment and parents/carers completing the Vineland Adaptive Behavior Scales. A cross-sectional trajectory analysis was conducted. There were significant WM span deficits in RTS relative to mental age. Verbal WM span was positively associated with mental age; however, this was not observed for visuo-spatial span. There is a dissociation between WM domains in RTS. Individuals may have difficulties with tasks relying on WM span, above difficulties predicted by overall ability.

Full text

ORIGINAL PAPER
Dissociation of Cross-Sectional Trajectories for Verbal
and Visuo-Spatial Working Memory Development in
Rubinstein-Taybi Syndrome
Jane Waite
1
•Sarah R. Beck
3
•Mary Heald
1
•Laurie Powis
2
•Chris Oliver
1
Published online: 24 March 2016
ÓThe Author(s) 2016
Abstract Working memory (WM) impairments might
amplify behavioural difference in genetic syndromes.
Murine models of Rubinstein–Taybi syndrome (RTS)
evidence memory impairments but there is limited research
on memory in RTS. Individuals with RTS and typically
developing children completed WM tasks, with partici-
pants with RTS completing an IQ assessment and par-
ents/carers completing the Vineland Adaptive Behavior
Scales. A cross-sectional trajectory analysis was con-
ducted. There were significant WM span deficits in RTS
relative to mental age. Verbal WM span was positively
associated with mental age; however, this was not observed
for visuo-spatial span. There is a dissociation between WM
domains in RTS. Individuals may have difficulties with
tasks relying on WM span, above difficulties predicted by
overall ability.
Keywords Working memory Short-term memory 
Rubinstein–Taybi syndrome Typically developing
children Dissociation
A growing body of research identifies impairments of
executive functions (EFs) as relevant to explaining
behavioural difference in people with genetic disorders
(Woodcock et al. 2009). Studies of associations between
specific cognitive profiles and behaviour can elucidate
possible pathways from genetic disorder to behaviour via
atypical brain development and interactions with the
environment (Woodcock et al. 2011). One component of
EF that warrants further investigation is working memory
(WM) (Wang and Bellugi 1994).
WM is served by two slave information processing
systems: the visuo-spatial sketchpad processes visual and
spatial information and the phonological loop processes
verbal information (Baddeley and Hitch 1974). A distinc-
tion is often made between simple and complex WM tasks.
Garon et al. (2008) define simple WM tasks as tasks
requiring a person to hold information in mind in either of
these systems (synonymous with short-term memory;
STM), while complex WM tasks require information to be
to manipulated and updated in WM. Compromised simple
or complex WM impact on the ability to act purposefully,
learn effectively and accomplish goals (Baddeley 1986).
There is evidence that these core information processing
systems (phonological loop and visuo-spatial sketchpad)
can be differentially impaired; lending support for the
separation of these systems in the classic model of WM
(Wang and Bellugi 1994). For example, individuals with
localised brain injury have shown greater impairment to
one system (Hanley et al. 1991), and interference from
competing cognitive tasks can impact these systems dif-
ferentially (Logie et al. 1990). In addition, dissociations
have been evidenced in the visuo-spatial sketchpad
between the processing of visual and spatial information
(Vicari et al. 2004).
Wang and Bellugi (1994) argued that one approach to
studying these dissociations is to explore WM profiles in
rare genetic syndromes. WM has been studied in rare
&Jane Waite
j.e.waite@bham.ac.uk
1
School of Psychology, Cerebra Centre for
Neurodevelopmental Disorders, University of Birmingham,
Edgbaston, Birmingham B15 2TT, UK
2
Specialist Learning Disability and Forensic Services,
Hertfordshire Partnership NHS Foundation Trust,
Hemel Hempstead, UK
3
School of Psychology, University of Birmingham,
Birmingham, UK
123
J Autism Dev Disord (2016) 46:2064–2071
DOI 10.1007/s10803-016-2736-2
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genetic syndromes and dissociations are reported. Jarrold
et al. (1999) found that individuals with William syndrome
performed poorly on simple visuo-spatial WM tasks rela-
tive to mental age (MA). However, relative strengths were
evident for simple phonological WM tasks. The opposite
pattern was found for Down syndrome. Other syndromes
might further inform this potential dissociation. A rela-
tively neglected syndrome in which WM impairments are
implicated from murine models but not yet explored in
humans is Rubinstein–Taybi syndrome (RTS).
RTS is a multiple congenital anomaly syndrome esti-
mated to occur in 1:100,000 to 1:125,000 live births and
most often associated with chromosome 16p.13.3; however,
genetic diagnosis is only possible in around 55 % of indi-
viduals. The majority of diagnoses are based on the physical
phenotype that includes short stature, downward slanting
perebral fissures, short ‘‘beaked’’ nose and broad thumbs
and toes (Hennekam 2006). Behavioural characteristics
include insistence on sameness, adherence to routine and
repetitive questions (Waite et al. 2015), with tentative evi-
dence of heightened social interest in RTS in comparison to
individuals matched on developmental level (Gale
´ra et al.
2009). Intellectual disability (ID) ranges from mild to sev-
ere, with expressive language delayed (Clarke and Langton
1992). Few cognitive and behavioural differences have
been identified between those with and without a geneti-
cally confirmed diagnosis (Bartsch et al. 1999). Murine
models have led to the proposal that ID may be underpinned
or exacerbated by impaired learning due to long-term
memory (LTM) deficits (Oike et al. 1999; Weeber and
Sweatt 2002; Wood et al. 2005); however, no published
studies have systematically investigated memory.
While it has been hypothesised that impaired LTM
underlies compromises learning in RTS, LTM is a single
component of a broader memory system. Models of
memory highlight that LTM interacts with WM. The suc-
cessful interaction of WM and LTM processes contributes
to knowledge acquisition and problem solving (Logie
1996). Additionally, WM and set-shifting have been linked
to repetitive behaviours, and an inability to recall words on
a STM task has been linked to perseverative speech in
dementia (Woodcock et al. 2009; Turner 1999; Cullen et al.
2005). In RTS, elevated levels of repetitive questioning
have been noted (Waite et al. 2015). One possibility is that
WM deficits are associated with repetitive questions. In this
study we focus on WM as the first step toward developing a
model of compromised memory underpinning impaired
learning and behavioural characteristics in RTS.
Studying WM development in RTS requires an appro-
priate comparison group. In TD children, WM has been
associated with the development of various abilities
including: vocabulary acquisition, reading comprehension,
mathematics, decision making and theory of mind (Bull
et al. 2008; Engle et al. 1999; Cain et al. 2004; Carlson
et al. 2002; Baddeley 1986). Understanding the WM profile
of RTS relative to TD children may lead to more specific
hypothesises concerning the relationship between memory
and other cognitive abilities in this syndrome. This
approach also enables consideration of whether individuals
with RTS have WM impairments aligned with global MA
or whether they have a profile of strengths and weaknesses
relative to MA. The principal aim of this study was to
explore the cross-sectional developmental trajectories of
working memory domains in RTS in comparison to TD
children.
Methods
Participants
RTS
Thirty-two participants with RTS were recruited (16 males;
mean chronological age: 221 months; chronological age
range 46–533 months; SD: 121.03). Of these, twenty-seven
were recruited from an existing database held by the
Cerebra Centre for Neurodevelopmental Disorders and five
via the RTS UK Support Group. Participants were included
if they were mobile and had a confirmed clinical diagnosis.
Eleven participants were excluded from analysis of the
WM tasks because they could not comprehend the task
instructions due to young age and/or severity of ID, or
because MA fell outside the range of the TD comparison
group. The mean chronological age of the remaining 21
participants was 232 months (9 males; age range
81–453 months; SD: 104.66). Of these participants, one
did not complete the Verbal Animal Span task due to poor
engagement.
TD Children
The TD comparison group comprised eighty-nine children
(mean chronological age: 62 months; 40 males; range
38–89 months; SD: 15.10) tested in schools in the West
Midlands, UK. Participants were included if they were not
identified by their class teacher as having a developmental
disability. To ensure a spread of ages, where possible, eight
TD children were tested in each 6 month age band between
38 and 89 months. TD data for the Scrambled Boxes tasks
were not collected beyond 78 months as the task was not
deemed developmentally appropriate.
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Measures
As moderate to severe ID is characteristic of RTS, delayed
EF development relative to chronological age would be
expected. Therefore, assessments were administered to
explore whether EFs were delayed/deviant relative to glo-
bal cognitive development (MA). Individuals with RTS
completed assessments of cognitive ability to ascertain MA
and three WM tasks.
Measures of General Cognitive Functioning
Participants with RTS completed the Mullen Scales of
Early Learning (MSEL: Mullen 1995), suitable for indi-
viduals from birth to 68 months. Participants at ceiling on
the MSEL completed the Wechsler Abbreviated Scales of
Intelligence—Second Edition (WASI-II: Weschler 1999),
suitable for individuals from 72 months–89 years. Stan-
dardised scores could not be derived for many participants
because, due to degree of ID, individuals completed the
MSEL despite being older than 68 months. MA equivalent
scores were calculated for the MSEL by calculating the
average of subscale scores from the receptive and expres-
sive language, visual reception and fine motor domains
(Richler et al. 2010). The gross motor domain was omitted
as the highest obtainable MA on this scale was lower than
the other scales. Similarly, MA was calculated for the
Wechsler Abbreviated Scales of Intelligence (WASI-II), by
averaging the MAs across sub-domains.
Adaptive Behaviour Assessment
The Vineland Adaptive Behavior Scales—Second Edition
(VABS-II; Sparrow et al. 2005) was included as an alter-
native measure of MA. This is a parent report measure of
adaptive functioning. There are no guidelines for comput-
ing global MA for the VABS. In the same manner as for
the psychometric assessments, global MA was calculated
by taking an average across the nine primary domains.
WM Test Selection and Administration
Tasks were selected from the developmental literature and
adapted to reduce receptive language demands. Two simple
WM tasks, the Verbal Animal Span and Corsi Blocks, were
included because pilot work indicated that individuals with
RTS had difficulty comprehending the rules for complex
WM tasks. One complex WM task, the Scrambled Boxes,
was included as it is suitable for very young children
(Carlson 2005). The WM tasks were administered as part
of a battery of EF tests constructed for a wider research
project and were administered in a fixed order. Deviations
from this order occurred for six participants who had
difficultly engaging with the verbal task first (order: Corsi
Blocks, Scrambled Boxes, Verbal Span). No significant
differences were found on task scores between these par-
ticipants and participants who completed the verbal span
task first (ps [.05).
Corsi Blocks (Pickering et al. 1998)
Participants were presented with a 20 925 cm white
board with ten 3.4 93.4 cm blue blocks mounted irregu-
larly. On each trial the researcher touched a sequence of
blocks starting with sequences of two. Participants
responded by touching the same sequence of blocks. After
two practise trials of two block sequences feedback was
given. Every three experimental trials the number of blocks
in a sequence increased by one. The task was terminated
after three consecutive incorrect trials. An adapted version
of a one point per pair coding scheme was adopted (Fudala
et al. 1974). For example, if the sequence was block 3,
block 6, block 7, block 2 and the response given is block 3,
block 6, block 7, block 2 then the paired item score was 3
(i.e. 3–6, 6–7 and 7–2). If the response was block 3, block
6, block 3, block 7 the paired score would be 1. Only
participants able to point to at least one block correctly on
each practise trial and who attempted to locate two blocks
in the correct order (demonstrating rule understanding)
completed experimental trials.
Verbal Animal Span (Adapted from Digit Span, Bull et al.
2004)
This task followed the same protocol and coding as the
Corsi Blocks task except participants verbally repeated
strings of animal names (all one syllable) after the exper-
imenter said them. This task was adapted from the tradi-
tional digit span for individuals less familiar with numbers.
Scrambled Boxes Task (Adapted from Diamond 1990)
Three versions of this task were included: Three, Six and
Nine Scrambled Boxes. The test equipment was eighteen
round wooden boxes (diameter =7 cm) each decorated
with a different shape, nine foam stars, a cardboard treasure
chest, a 29.7 942 cm cardboard screen and two cardboard
baseboards that indicated where the boxes should be
positioned in each task. Boxes were positioned 5 cm apart
for the Three Scrambled Boxes and 8 cm apart for the Six
and Nine Scrambled Boxes task respectively. In all ver-
sions, participants watched the experimenter put a star in
each box and close them. Participants were asked to find
stars and put them in a treasure chest. Once a box was
selected and the star removed, the empty box was returned,
the boxes were hidden behind the screen and the positions
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of the boxes were scrambled by the researcher. The boxes
were scrambled for 5 and 10 seconds in the three and six/
nine Scrambled Box task respectively. Participants then
searched again.
The Six Scrambled Boxes task was administered first. If
a participant retrieved all six stars without error the task
was repeated using nine boxes and a full score was given
for the three box task. If an error was made the task was
repeated with three boxes and a score of zero given on the
nine box task. Maximum scores for the Three, Six and Nine
Scrambled Boxes tasks were four, seven and ten respec-
tively, with one point lost for each incorrect reach. The task
was terminated if the participant lost all their points. A
composite scaled score was calculated by summing scores
from the three tasks.
Data Analysis
Validity of MA Equivalent Scores and Association
with CA
Mean age equivalent score for the total RTS group
(N =32) on the direct cognitive assessments (MSEL and
WASI) was 61.83 months (SD: 34.20). Mean age equiva-
lent score on the indirect informant report measure (VABS-
II) was 65.89 months (SD: 37.16). A Wilcoxon test
revealed no significant differences between these scores.
The intraclass correlation coefficient between the direct
and indirect MA equivalent scores was calculated to
measure the level of agreement: .91 (95 % CI Lower =
.82, Upper =.96, (df: 30, 30), F =21.41, p\.001).
Given the high level of convergence between MA equiv-
alent estimates, only scores from the direct assessments
(MSEL and WASI) were used in further analyses.
To aid interpretation of MA cross-sectional trajectories a
linear regression was conducted to explore associations
between MA (MSEL and WASI) and CA in RTS. A
straight line fitted these data (R
2
=.41, F(1,30) =20.50,
p\.001) with an intercept of 4.18 and a gradient of 0.27;
95 % CI 2.31–5.83).
Analysis of WM Tasks
As development is a dynamic process, traditional group
comparisons that match a syndrome group to a control
group can obscure important changes in the cross-sectional
developmental trajectory of the syndrome group (Karmil-
off-Smith 1998; Thomas et al. 2009). For example, if there
is a peak in performance at a particular age followed by a
decline this may be obscured when a group average is
taken. Thomas et al. (2009), Thomas (2010) described how
linear cross-sectional trajectory analysis, involving the
graphical representation of all data points, can aid under-
standing cognitive development whilst overcoming the
limitations of matching. This methodology was applied to
data obtained from the simple WM tasks. Data from the
Scrambled Boxes task were not appropriate for linear
cross-sectional trajectory analysis so independent t-tests
were conducted, with an alpha level of .01 to correct for
multiple tests.
Prior to the between groups linear cross-sectional tra-
jectory analysis, regression lines were fitted to the simple
WM task data for each group. Between Groups linear
cross-sectional trajectory analysis compares the intercepts
(onset of the lines) and gradients (slopes of the lines) of
two cross-sectional trajectories that are plotted as a func-
tion of age to ascertain whether the trajectories differ for
the two groups at the earliest age of measurement (equiv-
alent of a main effect of group), and whether age may
differentially impact on the two groups. The analysis was
conducted as described by Thomas et al. (2009), Thomas
(2010) by making an adaption to the Analysis of Covari-
ance function within General Linear Model (ANCOVA).
Typically, including two groups with different cross-sec-
tional trajectories in an ANCOVA is a violation of the
test’s assumptions because ANCOVA computes one
regression function during the analysis; however, by add-
ing an interaction term to this model (group 9age) it is
possible to compare the slope of the two cross-sectional
trajectories. The x-axis was rescaled prior to the analysis so
that the intercept of the regression lines would represent
scores at the youngest age of measurement. Further details
on this method are available at: http://www.psyc.bbk.ac.uk/
research/DNL/stats/Thomas_trajectories.
Results
The descriptive statistics for the WM tasks are displayed in
Table 1with linear cross-sectional trajectories for the
Verbal Animal Span and Corsi Blocks displayed in Fig. 1.
Verbal Animal Span Cross-Sectional Trajectory
Initial regression analyses indicated that a straight line
fitted the RTS data, R
2
=.31, F(1, 18) =8.04, p=.01,
with an intercept of 5.30 and gradient of 0.16, and the TD
data, R
2
=.24, F(1, 87) =27.85, p\.001, with an
intercept of 13.61 and gradient of 0.28.
The adapted ANCOVA indicated that a significant
proportion of the overall variance was explained by this
model, F(3,105) =26.59, p\.001, =.43. There was a
8.31 point score difference between the intercepts of the
TD and RTS and TD trajectories, F(1,105) =5.95,
p=.016, g
2
=.05. When the TD and RTS groups were
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combined, MA significantly predicted score on the Verbal
Animal Span, F(1,105) =11.17, p=.001, g
2
=.10;
however, there was no significant age x group interaction,
F(1,105) =.94, p=.334, g
2
=.01. Thus, the significant
score difference between the groups remained consistent
across the age range.
Corsi Blocks Cross-Sectional Trajectory Analysis
Linear regression analyses revealed that a straight line fit-
ted the TD Corsi Blocks data (R
2
=.49, F(1, 87) =82.78,
p\.001), with an intercept of 2.81 and gradient of .43. A
straight line did not fit the RTS data [R
2
=.02, F(1,
19) =0.46, p=.505] but this was due to the flat cross-
sectional trajectory (see Fig. 1). The cross-sectional tra-
jectory had intercept of 3.38 and gradient of .05.
The adapted ANCOVA indicated that a significant
proportion of the overall variance was explained by this
model, F(3,106) =.17.79, p\.001, =.14. The RTS and
TD scores were not significantly different at the youngest
age of measurement (intercepts) on the cross-sectional
trajectory, F(1,106) =.05, p=.837, g
2
\.01. There was
significant group 9age interaction, F(1,106) =13.23,
p\.001, g
2
=0.11. The RTS cross-sectional trajectory
appears flat, while the TD cross-sectional trajectory has a
positive slope with age (see Fig. 1).
The point at which the 95 % confidence intervals no
longer overlap (see Fig. 1) indicates that the cross-section
trajectories are reliably different at 49 months.
Scrambled Boxes Analysis
There were no significant differences between the RTS and
TD groups on the Three Scrambled Boxes, t(22.65) =
1.54, p=.137, d=0.22, Six Scrambled Boxes,
t(25.02) =1.78, p=.087, d=0.50, or Nine Scrambled
Boxes, t(38.20) =1.78, p=.140, d=0.33. Using our
adjusted alpha level the total score also failed to reach
significance, t(107) =2.31, p=.039, d=0.50. In addi-
tion, no significant correlations between performance and
MA were found.
Discussion
This study explored the development of WM in RTS rel-
ative to MA using cross-sectional trajectory methods
Thomas et al. (2009), Thomas (2010). MA was calculated
by averaging MA equivalent domain scores from the
MSEL and, while this method is likely to only provide a
gross estimate of MA, the MAs appeared to have conver-
gent validity with MA estimates from an informant
assessment (VABS). Cross-sectional trajectories were then
presented for verbal and spatial span tasks. The results
indicated that WM span may be compromised in RTS but
performance was variable across tasks depending on the
aspect of WM measured.
Findings suggest that in RTS verbal and visuo-spatial
WM span may be compromised relative to MA. This is
illustrated by the Animal Span task and the Corsi Blocks
cross-sectional trajectories as performance on these tasks is
below that of the TD group. Despite this, there are some
differences between cross-sectional trajectories. On the
verbal span task, TD children consistently outperform the
Table 1 Descriptive statistics (mean, SD & range) on working
memory tasks for RTS and TD group
RTS (N =21) TD (N =89)
Mean (SD) Range Mean (SD) Range
Verbal animal span 8.75 (3.67) 0–17 20.36 (8.56) 6–51
Corsi blocks task 4.05 (2.78) 0–10 12.98 (9.09) 0–37
Scrambled boxes
task—Composite
Score
8.14 (5.72) 4–21 10.95 (5.50) 2–21
R² = 0.2425
R² = 0.3085
0
10
20
30
40
50
60
35 45 55 65 75 85 95
Score on Verbal Animal Span
Age (TD = CA; RTS = MA)
TD
RTS
R² = 0.4876
R² = 0.0237
0
10
20
30
40
50
60
35 45 55 65 75 85 95
Score on the Corsi Block Task
Age (TD: CA; RTS: MA)
TD
RTS
Fig. 1 RTS and TD trajectories for scores on the span tasks as a
function of MA
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individuals with RTS. While the RTS group lags behind the
TD group, individuals with RTS who had higher MAs
performed better than those with lower MAs. The design is
cross sectional so change over time cannot be assumed;
however, a moderate association between MA and
chronological age suggests improvement in verbal span
with chronological age in RTS. The Corsi block span
shows a different pattern whereby there is initial overlap of
the RTS and TD cross-sectional trajectories at the youngest
age of measurement (MA) but the RTS trajectory remains
flat in contrast to the positive slope for the TD group. In
addition, a proportion of individuals with RTS were not
able to score on the experimental trials of this task (re-
quiring them to retain two items in memory) despite
understanding the rules of the task and memorising at least
one block during the practise phase.
Not all of the results suggest WM impairments in RTS
because the groups did not differ on the Scrambled Boxes
task, a visuo-spatial WM task. During this task participants
are required to remember distinct objects that vary on two
memorable dimensions (colour and shape) and this may be
less demanding than the Corsi block task that requires the
tracking of movement. There is evidence that tracking
movement has different neurological correlates than
remembering shape and colour, so these results may rep-
resent a dissociation of the visuo-spatial sketchpad (Vicari
et al. 2003; Logie 1996). Alternative interpretations are that
interacting with the boxes for a longer time or the imme-
diate reward from receiving stars may form stronger
memory representations (Vogel et al. 2006), or that the
recognisable shapes on the boxes led to some verbal
encoding and aided performance. Finally, a conservative
alpha level was used in the scrambled boxes analysis to
correct for multiple tests, so it remains possible that group
differences could exist on this task. As with all these tasks,
further investigation is necessary to extrapolate to the
mechanisms underlying performance.
As noted previously, it has been proposed that ID
associated with RTS may be linked to mutations in the
CREB binding protein and the effects on LTM associated
with hippocampal functioning (Oike et al. 1999; Weeber
and Sweatt 2002; Wood et al. 2005). A number of studies
with knock-out mice have explored the link between these
mutations and phenotypic characteristics, and while these
mice develop LTM difficulties, STM is not affected (see
Josselyn (2005) for a review). It has been be argued that
simple WM tasks, such as those included in the current
study, can only be defined as STM tasks because of the
absence of an updating component (Gathercole and Allo-
way 2006). Therefore, the poor performance of the RTS
group on simple WM tasks does not fit neatly with murine
models of RTS. Instead, these results point to a possible
double deficit of memory function.
A syndrome comparison group was not included in this
study but the RTS memory profile is likely to be pheno-
typic because WM lags behind overall ability. The memory
profile in RTS appears different to other syndrome groups.
For example, in Down Syndrome visuo-spatial skills are a
relative strength, whereas in William syndrome they are a
weakness relative to verbal skills (Jarrold et al. 1999).
Individuals with RTS evidence difficulties in both domains.
The results of this study will inform clinicians and
teachers working with RTS. External memory aids may be
particularly useful for helping individuals remember
information sequences and it may be helpful to present
information in no more than two–three chunks at a time.
The results suggest that older individuals with RTS are
likely to have more developed verbal WM spans and fur-
ther studies could explore the possibility of accelerating
development of verbal WM capacity using computerised
tasks that train this ability, as has been demonstrated pre-
viously (e.g. Klingberg et al. 2005). Finally, it would be
interesting to consider WM deficits in RTS in relation to
other aspects of the behavioural phenotype such as the high
levels of repetitive questioning noted in this group (Waite
et al. 2015).
As this is the first study of memory in individuals with
RTS, there are inevitably some limitations. Firstly, despite
the convergence of MA across assessments, MA can only
be taken as an estimate for examining gross dissociations in
cross-sectional trajectories at group level. In addition, it is
only possible to draw conclusions within the develop-
mental window between 38 and 89 months. Performance
of individuals with MAs outside this window may not map
onto these cross-sectional trajectories. In addition, partici-
pants with RTS would need to be followed up to confirm
whether higher performance on verbal span tasks in those
with higher MA represents developmental change. Finally,
the MSEL and VABS were not completed by the TD
comparison group due to constraints of testing in schools.
However, the sample of children was large, increasing the
likelihood of a MA cross-sectional trajectory accurately
reflecting the ability of the TD group.
Order effects may have occurred from fixed order
administration. It could be argued that poor performance on
the Corsi span task represents general fatigue and disen-
gagement. There was no statistical difference, however,
between the small subset of individuals who received the
Corsi block span first. Furthermore, all 21 participants went
on to complete a broader EF battery as part of a wide scale
study without demonstrating a drop off in performance that
characterised the Corsi block span; therefore, these results
appear robust. A further limitation of the Corsi block span
is that it may not discriminate well between the two groups
at the youngest ages since all children were at or near the
floor of the task. Overall, these results are an encouraging
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first step towards profiling memory in a syndrome in which
memory impairments would be anticipated given murine
models (Oike et al. 1999; Wood et al. 2005). In addition,
these results lend further support to a dissociation of the
phonological loop and visuo-spatial sketchpad. A differ-
ence in performance also was found between groups on the
Corsi Blocks task but not the Scrambled Boxes task. Whilst
these differences may be due to the nature of the tasks
used, this provides tentative evidence of a dissociation
between spatial processing (e.g. tracking movement) and
visual processing in the (e.g. colours and shapes) in the
visual spatial sketchpad and concurs with previous research
(Logie 1996, Vicari et al. 2003). Exploring the neurological
correlates of performance on these WM tasks in individuals
with RTS could provide further evidence for the dissocia-
tion of these abilities (Vicari et al. 2003).
Acknowledgments We are grateful to our funding body, Cerebra,
and the Rubinstein–Taybi Syndrome Support Group. We are grateful
to Hayley Crawford, Amsa Iqbal and Ruchi Bakshi for assistance with
data collection and coding.
Author Contributions JW, SRB, MH, LP and CO conceived the
study, participated in its design and coordination, analysis and
interpretation of data, drafted the manuscript, and revised it for
important intellectual content. All authors read and approved the final
manuscript.
Compliance with Ethical Standards
Conflict of interest The authors have no financial or other interests
related to the research in this manuscript.
Ethical Approval This study was approved by the NHS Coventry
and Warwickshire Research Ethics Committee.
Open Access This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://crea
tivecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
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