Neuroscience Letters 405 (2006) 24–28

Articulatory rehearsal in verbal working memory: A possible

neurocognitive endophenotype that differentiates between
schizophrenia and schizoaffective disorder
∗
Oliver Gruber , Eva Gruber, Peter Falkai
Cognitive Neuroscience Unit, Department of Psychiatry and Psychotherapy, Saarland University Hospital, Homburg (Saar),
Germany
Received 26 April 2006; received in revised form 8 June 2006; accepted 9 June 2006

Abstract
Recent fMRI studies have identified brain systems underlying different components of working memory in healthy individuals. The aim of
this study was to compare the functional integrity of these neural networks in terms of behavioural performance in patients with schizophrenia,
schizoaffective disorder and healthy controls. In order to detect specific working memory deficits based on dysfunctions of underlying brain circuits
we used the same verbal and visuospatial Sternberg item-recognition tasks as in previous neuroimaging studies. Clinical and performance data
from matched groups consisting of 14 subjects each were statistically analyzed. Schizophrenic patients exhibited pronounced impairments of
both verbal and visuospatial working memory, whereas verbal working memory performance was preserved in schizoaffective patients. The
findings provide first evidence that dysfunction of a brain system subserving articulatory rehearsal could represent a biological marker which
differentiates between schizophrenia and schizoaffective disorder.
© 2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: Functional neuroanatomy; Brain imaging; Schizophrenia; Pathophysiology; Neurocognitive endophenotype

There is a continuing debate on whether schizoaffective dis-
order represents a diagnostic entity that can be biologically
distinguished from schizophrenia [7,13,16,21,23].
Comparative neuropsychological studies of patients with these
two diagnoses may help to clarify this issue. While there is
an abundance of neuropsychological investigations in
schizophrenic patients indicating a broad range of cognitive
impairments with a focus on working memory, attention and
problem-solving [2,12,15], little is known about
neurocognitive deficits in schizoaffective patients. Existing
evidence suggests that schizoaffective patients exhibit a pattern of
cognitive impairments very similar to the one observed in
schizophrenia [2].
In particular, schizoaffective patients did not perform
signif- icantly different from patients with schizophrenia in a
number of classical neuropsychological tasks measuring
various aspects of memory, executive functions, cognitive
flexibility, reasoning and problem-solving [1,4,7,17,18,22].
However, this evidence is still very limited as most of the tasks
that were used in these stud-
∗
Corresponding author. Tel.: +49 6841 16 24245; fax: +49 6841 16 24270.
E-mail address: oliver.gruber@uniklinikum-saarland.de (O. Gruber).
ies cover a variety of cognitive functions. As a result these
tasks are reasonably sensitive to cognitive impairments, but
they lack specificity for detecting more selective dysfunctions
of neural systems that underlie single cognitive processes. Just
recently, researchers have begun to apply more refined task
paradigms derived from experimental cognitive psychology in
order to determine cognitive dysfunctions in a more specific
way [7]. Furthermore, due to the advent of functional brain
imaging tech- niques it has become possible to identify brain
regions involved in the single cognitive processes that are
necessary to perform these experimental tasks. Combining
functional brain imaging in healthy human subjects and
experimental neuropsychologi- cal investigation in patients
may prove helpful in discovering the neuropathophysiological
mechanisms of different psychi- atric disorders.
Working memory dysfunctions are a promising candidate
endophenotype that may enlighten schizophrenia research
field as to the genetic and other etiologic factors [3,6]. Recent
functional neuroimaging studies have shown with high con-
sistency that distinct brain systems underlie different working
memory components in humans [8–11]. The aim of the present
study was to compare the functional integrity of these neural

0304-3940/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights
reserved. doi:10.1016/j.neulet.2006.06.062
 O. Gruber et al. / Neuroscience Letters 405 (2006) 24– 25
28
networks in patients with schizoaffective disorder, in patients Table 1
with schizophrenia as well as in healthy controls. In order to Sample demographic and clinical variables
attribute working memory deficits observed in the patients
Schizophrenia Schizoaffective Control
to specific neural network dysfunctions, the present study Number of 14 14 14
employed the same experimental design as used in one of our subjects Gender 64.3 64.3 64.3
(% female)
previous fMRI studies [11]. Age at evaluation 37.8 (9.2) 38.4 38.9 (8.6)
(8.3)
Fourteen schizoaffective and 31 schizophrenic inpatients Education (y) 13.7 (3.5) 13.7 13.7 (2.7)
(3.3)
were recruited from the Psychiatric Department at Saarland Uni- Age at onset 30.6 (7.6) 26.4 (5.8)
–
Duration of illness (y) 7.2 (8.5) 11.9 (6.5)
–
versity Hospital. Inclusion criteria for patients were diagnosis
of schizoaffective disorder or schizophrenia according to ICD- Symptom severity
CGI 3.8 (1.3) 3.8 –
10 and DSM-IV criteria and age range from 18 to 65 years. (1.0)
Due to weak diagnostic reliability, in particular during the ini- PANSS positive 11.1 (5.1) 10.9 –
tial diagnosis of schizoaffective disorder, differences between (6.5)
PANSS negative 12.1 (3.4) 10.6 –
patient groups may obscure [13]. Therefore, we only included Medication type
patients with at least three prior hospital admissions that ful- Neuroleptics
filled the aforementioned criteria based on a consensus of several Typical only 2 0 –
experienced clinicians including the supervision by two senior Atypical only 12 10 –
researchers. Exclusion criteria were acute suicidality, involun- Both types 0 4 –
Approximated daily 316 485 –
tary treatment, current substance abuse, history of brain
CPZ equivalents
trauma, diseases with alterations of cerebral metabolism, Mood stabilizers
uncorrected
visual or auditory disability and mental retardation. Criteria Lithium 0 1 –
for Other 0 10 –
recruitment of 41 healthy comparison subjects were the same Antidepressants 1 6 –
as for patients plus the absence of any past or present Benzodiazepines 5 5 –
psychiatric disorder. All subjects gave written informed Anti-Parkinson agents 2 0 –
consent. None (unmedicated) 0 0 14
Experimental neuropsychological testing was performed
under standardized laboratory conditions. The behavioural
experiment consisted of four tasks, testing for different types 39) = 4.95, p < 0.05) as well as a trend for between-group effects
of working memory functions, i.e. articulatory rehearsal, non- in the two visuospatial task conditions (visuospatial “rehearsal”:
articulatory maintenance of phonological information, visu- F(2, 39) = 2.63, p < 0.1; visuospatial pattern maintenance: F(2,
ospatial “rehearsal” and maintenance of visuospatial patterns. 39) = 2.46, p < 0.1). Bonferroni-corrected post-hoc contrasts
The order of the tasks was counterbalanced across subjects. indicated a significantly reduced performance of
For a detailed description of the experimental paradigm, the schizophrenic patients in the articulatory rehearsal task
stim- ulation protocol and the task instructions see Gruber and compared to both healthy controls (p < 0.001; d (effect size
von Cramon [11]. The clinical state of the patients was index) = 0.86) and schizoaffective patients (p < 0.005; d = 0.77;
assessed at the day of the experiment using clinical global see Fig. 1D). On the contrary, schizoaffective patients did not
impression scale (CGI), montgomery asberg depression scale show a reduction of performance in comparison with healthy
(MADRS), positive and negative syndrome scale (PANSS). controls (p = 1.0; d = 0.09). In the second verbal working
After obtaining data from 14 patients with schizoaffective memory task test- ing for non-articulatory maintenance of
disorder, out of the groups of 31 schizophrenic patients and 41 phonological informa- tion, schizophrenic patients performed
healthy control subjects subgroups were recruited that significantly worse than healthy controls (p < 0.05; d = 0.61)
matched the schizoaffective patients regarding gender, age whereas no difference was observed between schizoaffective
and educa- tional status. Statistical analyses were carried out patients and healthy controls (p = 1.0; d = 0.13). Direct
using SPSS for Windows. comparison between schizophrenic
Demographic and clinical characteristics of the patient and
control groups are shown in Table 1. As a result of careful match- Table 2
Accuracy on the different working memory tasks (mean percentage of correct
ing, the three groups of 14 subjects each did not differ from
answers and standard deviation)
each other with regard to age (F(2, 39) = 0.06, p = 0.94), gen-
der (p = 1.0) or years of education (p = 1.0). The two patient Schizophrenia Schizoaffective Control
(n = 14) (n = 14) (n =
groups were also highly comparable regarding psychopatholog-
14)
ical symptoms according to the rating scales.
Behavioural performance data as shown in Table 2 were Articulatory rehearsal 81.9 ± 11.6 92.8 ± 4.6 94.0 ± 4.5
nor-
mally distributed except of the percentage of correct responses group Non-articulatory maintenance of phonological
in the visuospatial “rehearsal” task (Kolmogorov–Smirnov information
test: p < 0.05). One-way ANOVA revealed significant between-
26 O. Gruber et al. / Neuroscience Letters 405 (2006) 24–
77.2 ± 11.2 85.1 ± 9.1 87.2 ± 5.6 28
effects in task performance for the two verbal task condi- Visuospatial “rehearsal” 83.4 ± 13.4 88.7 ± 8.6 91.7 ± 5.6
tions (articulatory rehearsal: F(2, 39) = 10.62, p < 0.001; non- Visuospatial pattern 81.4 ± 12.9 80.5 ± 15.8 90.0 ± 7.2
articulatory maintenance of phonological information: F(2, maintenance
Fig. 1. Brain systems underlying specific components of human working memory (A: Articulatory rehearsal; B: Non-articulatory maintenance of phonological
information; C: Visuospatial working memory, i.e. both visuospatial “rehearsal” and visuospatial pattern maintenance) [11] and dysfunctions of these brain
systems indicated by performance deficits in matched groups of patients with schizophrenia and schizoaffective disorder (D).

and schizoaffective patients revealed a trend for a minor per-
formance in the former group (p = 0.07; d = 0.48). Furthermore,
in the visuospatial “rehearsal” task there was also a statistical
trend for reduced performance of schizophrenic patients as com-
pared to healthy subjects (p = 0.09; d = 0.46) whereas differences
between schizoaffective and schizophrenic patients (p = 0.46;
d = 0.30) as well as between schizoaffective patients and healthy
controls (p = 1.0; d = 0.17) were not significant. Finally, both
groups of patients showed reduced performance in the visu-
ospatial pattern maintenance task. However, due to a high
inter- individual variability these performance reductions did not
reach
the level of significance (schizophrenic patients versus con-
trols: p = 0.23; d = 0.37; schizoaffective patients versus controls:
p = 0.15; d = 0.41; schizophrenic versus schizoaffective patients:
p = 1.0; d = 0.04).
Because the assumption of normality of performance data
was not met for all experimental task conditions (see above), the
results of the parametric statistical tests were confirmed by
non- parametric tests. Using the Kruskal–Wallis test we
confirmed the significance of between-group effects in verbal
working mem- ory task performance (articulatory rehearsal: p <
0.005; non- articulatory maintenance of phonological
information: p < 0.05)
whereas between-group effects in the visuospatial working
memory tasks did not reach the level of significance (visuospatial
rehearsal: p = 0.29; visuospatial pattern maintenance: p = 0.12).
Mann–Whitney tests confirmed the reductions of verbal work-
ing memory performance in schizophrenic patients compared
to healthy controls (articulatory rehearsal: Z = 3.02, p = 0.002;
non-articulatory maintenance of phonological − information:
Z = 2.58, p = 0.009) as well as to schizoaffective patients (artic-
− rehearsal: Z = 2.79, p = 0.004; non-articulatory main-
ulatory
tenance of phonological−information: Z = 2.00, p = 0.04).
Taken together, schizophrenic patients − exhibited marked
deficits in both verbal and visuospatial working memory. By
contrast, verbal working memory performance was preserved
in a matched group of schizoaffective patients (Table 2, Fig.
1D). A series of functional MRI studies has reliably
demonstrated that different dissociable brain systems subserve
working mem- ory performance in the same tasks as used in
the present study [8–11]. Based on these prior findings, the
present study suggests that the functional integrity of a left-
hemispheric premotor- parietal network underlying the
articulatory rehearsal mech- anism (Fig. 1A) is disturbed in
terms of impaired perfor- mance in the majority of patients
with schizophrenia, but not in patients with schizoaffective
disorder. This difference can- not be attributed to effects of
age, gender, educational status, psychopathological symptoms
or medication (see Table 1).
The findings of this study are in line with prior neu-
ropsychological investigations of schizophrenic patients pro-
viding evidence for impairments of both verbal and visuospa-
tial working memory [3,5,6,14,19,24]. The outcome regard-
ing schizoaffective patients is not fully consistent with the
literature as several investigators reported similar cognitive
impairments in both schizoaffective and schizophrenic
patients [1,4,7,17,18,22]. However, the methodical
comparability of these studies is very limited, and none of
these prior investiga- tions employed tasks derived from
experimental psychology and functional neuroimaging that
specifically assess dysfunctions of the articulatory rehearsal
mechanism. While from the present study alone one cannot
exclude a general verbal cognitive deficit in the schizophrenic
patients as compared to the schizoaffective patients, this seems
to be unlikely in the light of these prior find- ings. In particular,
a previous study which directly addressed general intellectual
functions and language measures in both schizophrenic and
schizoaffective patients did not show any evi- dence for
differences between the patient groups [22]. Hence, our
finding of a significant difference between schizophrenic and
schizoaffective patients in verbal working memory perfor-
mance indeed suggests a more specific deficit of
schizophrenic patients in articulatory rehearsal. By contrast, in
the visuospa- tial working memory task under conditions of
interference we observed reduced performance rates both in
schizophrenic and schizoaffective patients which is in
accordance with previous findings [7].
Information based on studies of healthy relatives and twins
of schizophrenic patients indicate that both verbal and visu-
ospatial working memory deficits may represent endopheno-
typic markers of schizophrenia [3,6,20]. The present findings
provide first evidence that dysfunction of a brain system sub-
serving articulatory rehearsal in verbal working memory is
common in schizophrenia, but not in schizoaffective disorder
patients, whereas both patient groups share deficits of visu-
ospatial working memory. Further investigations in a higher
number of subjects as well as in relatives are required in order to
explore whether characterization of patients according to these
neurocognitive parameters may facilitate the development of a
neurobiological classification of psychiatric disorders.
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