A comparative study of the working memory multicomponent model in psychosis and healthy controls Ana M. S´anchez-Torres, M. Rosa Elos´ua, Ruth Lorente-Ome˜naca, Luc´ıa Moreno-Izco, Manuel J. Cuesta PII: DOI: Reference:
S0010-440X(15)00083-8 doi: 10.1016/j.comppsych.2015.05.008 YCOMP 51520
To appear in:
Received date: Revised date: Accepted date:
19 January 2015 4 May 2015 21 May 2015
Please cite this article as: S´anchez-Torres Ana M., Elos´ ua M. Rosa, Lorente-Ome˜ naca Ruth, Moreno-Izco Luc´ıa, Cuesta Manuel J., A comparative study of the working memory multicomponent model in psychosis and healthy controls, Comprehensive Psychiatry (2015), doi: 10.1016/j.comppsych.2015.05.008
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ACCEPTED MANUSCRIPT TITLE: A COMPARATIVE STUDY OF THE WORKING MEMORY MULTICOMPONENT MODEL IN PSYCHOSIS AND HEALTHY CONTROLS AUTHORS: Sánchez-Torres, Ana M.a, b, c, Elosúa, Mª Rosac, Lorente-Omeñaca, Rutha, b, c, Moreno-Izco, Lucíaa, b, Cuesta, Manuel J. a, b b c
Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain IdiSNA, Navarra Institute for Health Research, Pamplona, Spain Department of Basic Psychology I, Universidad Nacional de Educación a Distancia (UNED), Madrid,
Manuel J. Cuesta Psychiatric Unit B, Complejo Hospitalario de Navarra c/ Irunlarrea, 4
+34 848 422488
+34 848 429924
e-mail: [email protected]
31008 Pamplona, Navarra
KEYWORDS: Working memory, Multicomponent model, Executive functions, Psychosis,
ACCEPTED MANUSCRIPT ABSTRACT Working memory deficits are considered nuclear deficits in psychotic disorders. However, research has not found a generalised impairment in all of the components of working memory. We aimed to assess the components of the Baddeley and Hitch working memory model: the temporary systems - the
phonological loop, the visuospatial sketchpad and the episodic buffer (introduced later by Baddeley) - and the central executive system, which includes four executive functions: divided attention, updating, shifting and inhibition. We assessed working memory performance in a sample of 21 patients with a
psychotic disorder and 21 healthy controls. Patients also underwent a clinical assessment. Both univariate and repeated measures ANOVA were applied to analyse performance in the working memory components between groups. Patients with a psychotic disorder underperformed compared to the controls
in all of the working memory tasks, but after controlling for age and premorbid IQ, we only found a difference in performance in the N-Back task. Repeated measures ANCOVAs showed that patients also underperformed compared to the controls in the Digit span test and the TMT task. Not all of the
components of working memory were impaired in the patients. Specifically, patients’ performance was impaired in the tasks selected to assess the phonological loop and the shifting executive function. Patients’ also showed worse performance than controls in the N-Back task, representative of the updating executive function. However, we did not find higher impairment in the patients’ performance respect to
controls when increasing the loading of the task.
ACCEPTED MANUSCRIPT 1. INTRODUCTION Working memory is an active system of storing information and information processing and is essential for the correct functioning of other complex cognitive functions. The model proposed by Baddeley and Hitch
is one of the most used models in neuropsychological research. In this model, the
working memory system includes four components: the phonological loop, which holds verbal information; the visuospatial sketchpad, which holds visual and spatial information; an episodic buffer that links the two prior components with long-term memory, and a central executive system. This system
addresses executive functions, such as the performance of two tasks simultaneously (divided attention), the selective attention to a stimulus and the interference inhibition of others, and the updating of incoming information as well as processing and maintaining information in the long term memory 4. 5, 6 7
Working memory deficits are considered nuclear features of schizophrenic disorders
contributing to other illness manifestations such as formal thought disorders. These deficits have been 8-10
, but also have been found in first-degree relatives of patients with
widely described in schizophrenia
psychosis and healthy subjects with schizotypal traits 11-14. However, research has not consistently found a generalised impairment of all of the components of working memory in patients with psychotic disorders 15-17. There are several methodological issues that make difficult to explore working memory functioning in psychotic disorders.
For instance, tasks more widely used to assess working memory and executive functions in 7
psychosis are complex and need more than one executive function to be solved. As Lee and Park
highlight in their meta-analysis, the trend in clinical research has been to use neuropsychological tests to
assess working memory which have not been specifically designed for this purspose. This is the case of the Wisconsin Card Sorting Test or the Hanoi Tower. Thus, tasks which allow separating the executive
functions implicated in working memory are needed 18, 19. The most widely used tasks to assess the phonological loop and the visuospatial sketchpad are
the digit span tasks and the spatial span or Corsi cubes tasks. Research has found a relatively unimpaired
performance in the digit span task in patients with schizophrenia controls
and also deficits with respect to
. In the spatial span tasks, patients with schizophrenia show difficulties in maintaining
. In contrast, when investigating working memory in psychosis within the
multicomponent model, the episodic buffer has received less attention. This component was proposed by Baddeley 2 years after the formulation of the Baddeley and Hitch working memory model. The episodic buffer was conceived as a multidimensional storage system that integrates information from long term memory, the temporary systems and perception, and is accessed through consciousness. Several experimental tasks (see
for a review) and standardised tests have been proposed to assess the episodic
buffer, such as verbal learning lists and phonemic and semantic fluency tests. Research using verbal learning lists is consistent in reporting deficits in verbal memory in patients with psychosis, even since the early phases of illness 21, 25, 26. These deficits could be a consequence of impairment of the episodic buffer. The central executive, as an attentional control system, deals with executive functions such as the performance of two tasks simultaneously, the selective attention to a stimulus and the interference inhibition of others, and the updating of incoming information, handling and maintaining it in the long term memory. As we reported above, it is difficult to find tasks that isolate these executive functions
ACCEPTED MANUSCRIPT separately. Here, we have selected a set of executive tasks that are representative of these four executive functions and have been studied in patients with a psychotic disorder. The dual task designed by Baddeley et al.
is one of the most commonly used to assess divided
attention in the central executive system. Dual tasks compare subjects' performance in the individual tasks
with subjects' performance when both tasks are conducted simultaneously. Patients with psychosis have shown worse performance in dual tasks compared to controls 15, 17, 28, 29.
Set shifting has been studied in patients with a psychotic disorder using the Trail Making Test 30, 31
. Low performance on the Trail
which has demonstrated low performance in first-episode psychosis
Making test has also been correlated with the presence of psychotic symptoms in bipolar disorder 32. Research in updating using N-Back paradigms has shown inconsistent results. These
inconsistent results may be happening because there is not a standardised paradigm. Patients with psychosis show more errors and higher reaction times when compared to controls
10, 33, 34
, but these results
are not comparable to each other because of the different methods of information loading in each paradigm.
One prototypical inhibition task is the Stroop test
, in which the subject must inhibit an
automatic reading response to concentrate on naming the colour of the items presented. Schizophrenia patients show more errors and lower response time than controls in this task
. Bora et al.
described impairment in this task in bipolar patients, which was associated with the presence of psychotic symptoms.
This study aimed to assess the working memory components of the Baddeley and Hitch model 1in patients with psychotic disorders compared to a healthy control group. We explored the three
temporary systems of the model - the phonological loop, the visuospatial sketchpad and the episodic
buffer - and the four executive functions included in the model: divided attention, set shifting, updating and inhibition. We formulated two hypotheses: patients with psychotic disorders would perform below controls in all of the working memory components, and the impairment would be larger in patients with
respect to controls when increasing the task difficulty, both in executive functions and in the temporary systems.
2. METHOD 2.1. Participants A total of 21 patients with a DSM-IV
psychotic disorder diagnosis were recruited from
consecutive admissions due to psychotic exacerbations to Psychiatric Unit B of the Complejo Hospitalario de Navarra in Pamplona, Spain. A control group of 21 healthy volunteers was also included. The inclusion criteria for participants were as follows: age between 16 to 50 years old, absence of history of head trauma, absence of drug dependence (except for tobacco), and IQ of 85 or higher. For the controls, we required the absence of a personal history, or history in first-degree relatives, of major psychiatric illness. All participants signed an informed consent form, and the study was approved by the local ethics committee. 2.2. Procedure
ACCEPTED MANUSCRIPT The assessments were conducted in two sessions, when patients had reached psychopathological stability, as part of a thorough study of cognition. The controls were assessed in one session of 1-1.5 hours. 2.2.1. Clinical assessments. The demographic and clinical variables were assessed with the 39
, a structured interview that assesses
Comprehensive Assessment of Symptoms and History (CASH)
current and lifetime psychopathology. For the purposes of this study, only current psychopathology was considered. Four psychopathological syndromes were obtained from the CASH: positive, negative, 40
and affective (mania and depression) dimensions. Patients' daily doses of antipsychotic
drugs were standardised to chlorpromazine equivalents 41.
2.2.2 Neuropsychological assessments. Seven cognitive tasks were chosen to assess the four
executive functions, the phonological loop, the visuospatial sketchpad and the episodic buffer. In addition, premorbid and current IQ were estimated with Wechsler Adult Intelligence Scale (WAIS-III) 42.
To estimated premorbid IQ, we used the standard scores (SS) of the Vocabulary subtest of the WAIS-III. The standard scores were converted to IQ scores with this formula: SS x 5 + 50. Current IQ was estimated with three subtests of the WAIS-III scale: Vocabulary, Similarities and Block design, following the guidelines of Sattler et al 43.
The Digit span and Spatial span subtests of the Wechsler Memory Scale-III
were used to
assess the phonological loop and the visuospatial sketchpad, respectively. The episodic buffer was assessed with the immediate and delayed recall tasks of the Screen for Cognitive Impairment in Psychiatry (SCIP-S)
purposes of this study.
. Raw scores of the Digit span, Spatial span and SCIP-S were used for the
Baddeley et al.’s
dual task was used to assess divided attention. The dual task consists of a
digit repetition task, adapted to the subject’s span previously assessed with the Digit span subtest, and a box-crossing task, in which participants are require to cross out boxes that form a path laid out on a sheet with 80 boxes as quickly as possible. First, the tasks are presented separately, and then the subject must
perform both tasks simultaneously, each part lasting 2 minutes. The distribution of attention, or mu index, reflects the percentage of performance in the dual task with respect to the single tasks and was calculated as follows: [1 - (pm + pt) / 2] x 100 (see Supplementary table 1). Shifting was assessed with the Trail Making Test (TMT) 30. Part A requires visuomotor speed,
and part B adds the set-shifting component. The index B/A was calculated to minimise the effects of motor speed. Updating was assessed with the N-Back 47. Participants were orally presented with a series of letters and were required to respond if the currently presented letter was the same as the one presented one (1-Back), two (2-Back) or three (3-Back) letters beforehand. Errors in each condition were recorded. To assess inhibition, the Stroop test 36 was used. It has three parts, each lasting 45 seconds: word reading, colour naming and incongruent naming. An interference score is calculated. 2.3. Data analyses The demographic characteristics between patients and controls were compared using t-tests and chi-squared tests.
ACCEPTED MANUSCRIPT We compared cognitive performance between groups with univariate ANOVAs. Demographic characteristics that were significantly different between groups were included as covariates. We also applied repeated measures ANOVAs including covariates. As each test included two or more conditions of increasing difficulty, these analyses allowed for ascertaining the patterns of
performance of both groups, considering the interaction of task by group as the indicator of each working memory component performance.
Partial correlations were calculated to assess the interrelationship between all of the working
memory components. For patients, the effects of treatment and psychopathology over cognitive performance were tested by calculating Pearson correlations.
3.1. Sample demographic characteristics
Patients and controls showed significant differences in age and estimated premorbid IQ. No significant differences were found in gender distribution and years of education (Table 1). [INSERT TABLE 1]
3.2. Neuropsychological tests
Premorbid IQ and age were introduced as covariates in all the ANOVAs. Table 2 shows the
scores selected to assess each of the working memory components. [INSERT TABLE 2]
The ANOVAs showed that patients underperformed compared with controls in each test score,
Back (Table 3).
but most of these differences disappeared when adding the covariates, except for the total errors of the N-
[INSERT TABLE 3] Table 4 shows the results of the repeated measures ANCOVAs. Patients underperformed
compared with controls in all of the tasks except for the Digit span and Spatial span tests and the digit
repetition task of the dual task. Task condition effects were significant in the Spatial span test and the TMT. In the Spatial span test, both groups underperformed on the backwards task compared to the forward test, and they also underperformed on part B of the TMT with respect to part A. Group x task interaction was significant for the Digit span test and for the TMT. That is, patients performed significantly worse than controls in the backward part of the Digit span when compared to the forward part, and part B of the TMT when compared to part A. Effect sizes (partial η2) showed that task per group interaction explained nearly 10-11% of the variance of task performance for the Digit span and TMT tasks. Slightly higher effect sizes were found when analysing task (Spatial span and TMT) and group effects (SCIP, N-Back and Stroop test). The difficulty of the task accounted for 13-14% of the variance, and the group accounted for 12-16% of the variance. Medium effect sizes according to Cohen
were obtained for task effects for the SCIP and N-
Back; group effects for the Digit span and digit repetition task; and interaction effects for the boxcrossing task and the Stroop test. However, none of these effects were significant in the ANCOVAs.
ACCEPTED MANUSCRIPT Figure 1 shows a graphical representation of the multicomponent model of working memory (Baddeley and Hitch, 1974; Baddeley, 1986, 2000), highlighting the components which appeared to be impaired in our patients’ sample.
[INSERT TABLE 4] [INSERT FIGURE 1]
3.3. Partial correlations between the temporary systems and executive functions In the patients’ group, the phonological loop and the visuospatial sketchpad tasks showed significant positive correlations. The episodic buffer and the updating executive function tasks showed
significant inverse correlations. No other significant correlation was found in the group of patients or in the controls (Table 5).
3.4. Treatment effects
[INSERT TABLE 5]
None of the correlations were significant. This result suggests that antipsychotic treatment was independent of working memory performance.
3.5. Effects of clinical symptoms in cognitive performance
The negative syndrome correlated with the total score of the Spatial span test (r = -0.54, p = .01), the total number of errors in the N-Back (r = 0.49, p = 0.02) and the mu index (r = -0.45, p = 0.04).
Positive, disorganised, depressive and manic symptoms did not correlate with working memory
3.6. Analysis of a subgroup of the total sample
The same statistical analyses were applied to a more homogeneous subset of patients (n=15) with a diagnosis of schizophrenia or schizoaffective disorder and controls (n=15) matched in age and years of education. Premorbid IQ was introduced as a covariate in the subsequent analyses after analysing
the demographic characteristics of this sample (Supplementary table 2). We only found different results when compared to the total sample in the TMT, but no significant effects of the task were found. With regard to the partial correlations between the temporary systems and executive functions, no significant results were obtained.
4. DISCUSSION Patients underperformed compared to controls in all the working memory tasks, but after controlling for age and premorbid IQ, only differences in the total number of errors in the N-Back test remained. In addition, the interaction task by group was significant for the Digit span task and the TMT, which are representative of two components of the Baddeley and Hitch working memory model: the phonological loop and the shifting executive function. These results partially confirm our hypothesis, as not all of the working memory components were impaired in the patients. These results cannot be attributed to the effects of treatment or symptoms, as we only found a relationship between more negative symptoms and worse performance in the tasks selected to assess the updating and divided attention executive functions and the visuospatial sketchpad.
ACCEPTED MANUSCRIPT In the phonological loop, patients showed a higher decline than controls when the manipulative component was added to the digit span task. Other authors have described a relatively preserved performance in the digit span task in forward order also found deficits in the backward order
, which is in agreement with our results, but have
in patients with psychosis.
Shifting executive function has been reported to be impaired since the early phases of psychotic 31
illness . The index B/A has been used by other authors to remove the processing speed component from the test execution
28, 31, 49, 50
. Although we did not find differences in this index, patients performed below
controls when the task's complexity increased. Therefore these differences cannot be explained only for a general processing speed deficit; they imply a shifting dysfunction.
In the N-Back task, representative of the updating executive function, patients showed
impairment in the total number of errors, but we did not find higher impairment in the patients’ performance when increasing the loading of the task. Deficits in updating in psychosis have been shown 10, 33, 51
. Broome et al.
to be related to the increase in the loading of the N-Back task
differential pattern of brain activation in the prefrontal and parietal cortex in an N-Back task between patients, subjects at high risk of psychosis, and controls, although the groups did not differ in the number of errors. Krieger et al.
reported impairment in the updating executive function in first episode
psychosis but only when a working memory load was imposed in an N-back task.
No specific impairment was found in the patients in the remaining working memory components. In the spatial span task, representative of the visuospatial sketchpad component, other studies have reported deficits in patients with schizophrenia in similar tasks
. We also found a
decline in performance in the backwards Spatial span task with respect to the forward task in both groups, which may be due to the involvement of the central executive functions in the performance of the
backwards tasks. This pattern of performance has been described in patients with bipolar disorders; patients with schizophrenia and schizoaffective disorders showed global impairment in both the forward and backward tasks 56. We found a domain-specific deficit of the verbal component, which contrasts with
Forbes et al. 57, who stated that Digit span and Spatial span tasks backwards can be regarded as relatively robust and reliable methods of identifying working memory deficits in schizophrenia. Regarding the episodic buffer,. Allen et al.
reported unimpaired performance in bipolar
patients in memory tasks that are dependent on the episodic buffer. They used tests of verbal and visual learning (California Verbal Learning Test and Biber Visual Learning Test), but they did not include a delayed recall task to assess the consolidation of the learned information. Studies with patients with schizophrenia using binding tasks have demonstrated impaired performance 59-61 and also an overall lower performance, not specifically in the binding processes
. Our results suggest that patients remembered
few words in the delayed recall because they held few words in the immediate learning task, pointing to a deficit in encoding verbal information rather than a dysfunction of the episodic buffer. Results in the tasks which represented the divided attention and inhibition executive functions revealed lower cognitive resources in the patients, which did not worsen when the tasks required the intervention of these executive functions. In the dual task, used to assess divided attention, patients performed below controls in the box-crossing task but not in the digit repetition task. Birkett et al.
attributed patients with schizophrenia underperformance to a lower level of general cognitive ability. This
ACCEPTED MANUSCRIPT pattern of results suggests that group differences may be related to non-attentional factors, such as processing speed or hand-eye coordination, which are necessary to perform the box-crossing task, rather than impairment of the central executive system itself. However, Oram et al.
performance in patients with schizophrenia in Baddeley’s dual task, but this worse performance was not
observed when patients performed a second task (tone counting and telephone search tasks performed simultaneously).
Research using the Stroop test has found that patients with psychosis have difficulty inhibiting 37
. Some studies, however, have attributed performance differences between
patients and controls to a slowdown in each of the parts of the test
, which may result in a non-
impaired interference index. To overcome this limitation, we also included a repeated measures analysis,
which confirmed an absence of impairment of inhibition.
There are methodological issues that make difficult to explore working memory functioning in
psychotic disorders. For instance, the tasks employed to assess working memory and executive functions are usually complex and need more than one executive function to be solved
. An interesting finding
is the independence of the four executive functions studied, assessed with partial correlations. We found an association of the phonological loop and the visuospatial sketchpad, and the episodic buffer with the updating executive function. These findings support the idea that executive functions are partially
independent; therefore, they may be assessed independently with specific tests 19, 66. Few studies have analysed all of the components of working memory as independent processes in patients with psychosis. Raffard and Bayard
examined the individual profiles of impairment in the
four executive functions in patients with schizophrenia. They concluded that even though the four executive functions were distinct constructs and differentially impaired in schizophrenia, this impairment
partially reflected the influence of general cognitive factors, such as premorbid IQ and processing speed. Other authors have also suggested that executive function impairments are due to a global cognitive impairment present before the onset of psychotic illness and not to impairments in specific cognitive
domains 17, 68.
Limitations This study has some limitations. The small sample size means that our conclusions cannot be
The sample was also heterogeneous in the diagnosis and course of illness, due to naturalistic recruitment. However, our results were similar when analyzing a more homogeneous subgroup of patients. The control group was not matched in premorbid IQ with the patients. This is a common limitation in studies with patients with psychosis because it may introduce a two-way bias: patients have either an abnormally high level of cognitive functioning, or the controls have an abnormally low level of cognitive functioning 69. To overcome this limitation, we chose to include premorbid IQ as a covariate in the analysis. It could be argued that using only one task to assess each of the working memory components of the Baddeley and Hitch model limits the scope of our results. However, we chose each task considering
ACCEPTED MANUSCRIPT its representativeness regarding the working memory component that we aimed to assess, and also its simplicity, to avoid the overlapping of cognitive functions in their execution. The study of chronic patients with psychosis implies the presence of confounding variables in the interpretation of results, such as treatment and symptoms' effects. However, cognitive deficits are
considered core manifestations of psychosis and are not related to pharmacological treatment Research has reported a moderate and nonspecific relationship between treatment and cognition
found no significant associations between antipsychotic doses and performance in executive functions.
Regarding symptoms, we only found significant correlations between negative symptoms and the spatial span test, N-Back and mu index. These associations did not explain our main results, since we did not found associations with the digit span test and TMT. Negative symptoms have been associated with
impairments in working memory and prefrontal cortex dysfunction in patients with psychosis 75-78. Indeed, it has been hypothesized that they both are a consequence of dysfunction of shared neural pathways, such
as dopamine hypoactivity in the prefrontal cortex 79.
We found a differential pattern of impairment in the components of the Baddeley and Hitch working memory model in our sample of patients with psychosis, compared to controls. These results
highlight the importance of exploring all the components with different representative tasks when
assessing working memory in patients with psychosis, since these components are partially independent.
ACCEPTED MANUSCRIPT ACKNOWLEDGMENTS
This work was supported by grants from the Government of Navarra (grant numbers 11/101 and 87/2014) and the Carlos III Health Institute of the Spanish Economic Affairs and Competitiveness (ERDF Funds) (grant numbers 08/I/1026 and 11/02831). We thank the subjects who took part in this study.
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ACCEPTED MANUSCRIPT Table 1. Demographic and clinical characteristics of the sample.
Years of education
Age at onset
Years since illness onset
Diagnosis n (%) 10 (47.62)
Delusional disorder Depressive disorder with psychotic symptoms Atypical antipsychotic dosesa
Estimated premorbid IQ
t or Chi-squared (p)
ACCEPTED MANUSCRIPT Table 2. Tests scores selected to assess each of the working memory components.
Digit Span test (total score)
Spatial Span test (total score)
SCIP word list (delayed recall)
Dual task (mu index)
Trail making test (B/A index)
N-Back (total errors)
Phonological loop TEMPORARY
Stroop Test (interference score)
attention Shifting Updating
1.42 (p =0.24)
7.41 (p =.003)*
0.61 (p =0.44)
Digit span (total)
Spatial span (total) SCIP (delayed recall)
N-Back (total errors) StroopInterference
Introducing age and premorbid IQ as covariates.
Table 3. Means and standard deviations of the neuropsychological tests and analysis of variance of the differences between patients and controls.
Digits span forward (max. 16)
Digit span backward (max. 14)
SS forward (max. 16)
SS backward (max. 16)
SCIP immediate recall (max. 10)
SCIP delayed recall (max. 10)
Digit span single
Digit span dual
TMT-A (time in seconds)
TMT-B (time in seconds)
Table 4. Repeated measures ANOVAs for each of the working memory components. Effect size
F=5.84 (p=0.02)* F=1.73 (p=0.2) F=6.37 (p=0.02)* F=5.1 (p=0.03)*
(Interaction: task x group)
Effect size (η2p)
SS: spatial span; SCIP: Screen for Cognitive Impairment in Psychiatry; TMT: Trail Making Test; Stroop-WC: Stroop word-colour a Introducing age and premorbid IQ as covariates * p<0.05
Partial correlations (controlling for
age and premorbid IQ)
Digit span (total
Spatial span (total
Spatial span (total score)
SCIP-S delayed recall
mu index (dual task)
N-Back (Total errors)
SCIP-S delayed recall
mu index (dual
Updating N-Back (Total errors)
Table 5. Partial correlations between executive functions and temporary systems for patients (n=21) and controls (n=21).
*p < 0 .05
ACCEPTED MANUSCRIPT Highlights
The components of the Baddeley and Hitch working memory model were assessed. Psychotic patients showed impairment in the phonological loop and shifting tasks. After controlling for age and premorbid IQ, no other impairments were found. An independence of the four executive functions studied was found. A subgroup of patients with schizophrenia or schizoaffective disorder showed similar results