Implications for visuospatial working memory archit

MEMORY, 2006, 14 (4), 437 /451

Executive and visuospatial sketchpad resources in euthymic bipolar disorder: Implications for visuospatial working memory architecture Jill M. Thompson University of Newcastle-upon-Tyne, UK C. J. Hamilton Northumbria University, Newcastle-upon-Tyne, UK John M. Gray University of Newcastle-upon-Tyne, UK J. G. Quinn University of St Andrews, UK Paul Mackin, Allan H. Young, and I. Nicol Ferrier University of Newcastle-upon-Tyne, UK Visuospatial working memory theory is used to interpret the cognitive impairment in euthymic bipolar disorder. Such patients show deficits in the Corsi Blocks Test (CBT) and executive control. To understand these deficits, 20 euthymic bipolar patients and controls were administered the CBT, Visual Patterns Test (VPT), and a new visual memory task designed to make minimal demands on executive resources. Initial analyses validated the visual memory task and implicated executive involvement in the CBT and VPT. Subsequent analyses on a number of tests confirmed CBT and executive deficits while performance was normal on the VPT and visual memory test. ANCOVA indicated that impaired executive function underpinned patients’ CBT performance. Implications for the interface between executive and slave systems of working memory are discussed.

Bipolar affective disorder is a recurrent, cyclical disorder that is characterised by alternating episodes of depression and mania, interspersed with periods of apparent recovery, or euthymia (Goodwin & Jamison, 1990). Kraepelin (1913) originally defined this condition partly on the

basis that it has remission between episodes. However, there is accumulating evidence that recovery in bipolar disorder is incomplete (Ferrier & Thompson 2002). Patients with bipolar disorder show persistent cognitive impairment during remission (for a

Address correspondence to: Dr Jill Maria Thompson, Department of Psychiatry, Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK. E-mail: [email protected] This project was supported by funding from the Stanley Medical Research Institute and the Mental Health Foundation. The project was part of Jill Thompson’s doctoral thesis. We thank Dr J. H. Hughes and Dr S. Watson for assistance with data collection. We also thank Drs C. Dracup and D. Knight for statistical advice, but would emphasise that the opinions expressed here (and any errors) remain our own. Finally, we are grateful to all of the participants who so generously gave up their time to participate in the research.

# 2006 Psychology Press Ltd http://www.psypress.com/memory

DOI:10.1080/09658210500464293

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review see Bearden, Hoffman, & Cannon, 2001). In accord with the neuroradiological and neuropathological data implicating morphological disturbance to fronto-subcortical and cortico-striatal circuitry (Bearden et al., 2001; Harrison 2002), performance deficits have been observed on several executive tests that are sensitive to frontal lobe function (Ferrier, Stanton, Kelly, & Scott, 1999; Hawkins, Hoffman, Quinlan, Rakfeldt, Docherty, & Sledge, 1997; Thompson et al., 2005; Zubieta, Huguelet, O’Neill, & Giordani, 2001). Working memory (WM) plays a prominent role in several theoretical accounts of executive function. For example, Baddeley and Hitch (1974) propose that WM is a multi-component system comprising an attentional control system, the central executive, aided by two subordinate systems, the phonological loop and the visuospatial sketchpad, which deal with the temporary storage and rehearsal of speech-based and visuospatial information respectively. Within this framework we have observed that euthymic bipolar patients show intact performance on measures tapping the phonological loop, but impaired performance on tasks tapping the central executive (Ferrier et al., 1999; Thompson, Gray, Hughes, Watson, Ferrier, & Young, 2000). On this basis, we have suggested that bipolar disorder is characterised by a specific and enduring deficit in the executive control of WM. However, such patients also show a deficit on a computerised version of the Corsi Blocks Task (CBT) (Thompson et al., 2000, 2005). Impaired performance on this sequential spatial span procedure is usually interpreted as a reduction in the capacity of the visuospatial sketchpad. There is now a substantial body of evidence that non-verbal WM is more heterogeneous than had previously been supposed, and may be divided into a purely visual component and a separate, but complementary, spatial processing system (reviewed by Logie, 1995). Neuroimaging studies in healthy adults, clinical lesion studies in humans, and studies of non-human primates suggest that these two types of information are processed by anatomically independent brain sites (Carlesimo, Perri, Turriziani, Tomaiuolo, & Caltagirone, 2001; Courtney, Petit, Maisog, Ungerleider, & Haxby, 1998; Wilson, Baddeley, & Young, 1999; Wilson, O’Scalaidhe, & Goldman-Rakic, 1993). Spatial and object WM have also been experimentally dissociated from one another in intact human subjects (Logie & Marchetti, 1991; Tresch, Sinnamon, &

Seamon, 1993), and have distinct developmental trajectories (Hamilton, Coates, & Heffernan, 2003; Logie & Pearson, 1997). Logie (1995) has developed a cognitive model of the visuospatial sketchpad to take account of the earlier findings. This comprises an active rehearsal mechanism (the inner scribe), which stores information about movement sequences, and a functionally distinct passive component (the visual cache), which stores information about visual form and colour. Logie’s model offers a useful extension of the concept of visuospatial working memory (VSWM), however any account of cognitive processes in WM is only as good as the tasks used to study these processes. Conventionally used span procedures such as the Corsi Block task (Milner, 1971) cannot be considered uncontroversial methods for sampling pure ‘‘visual’’ and ‘‘spatial’’ WM, as evidence is emerging that these measures also recruit executive resources (Fisk & Sharp, 2003; Hamilton et al., 2003; Klauer & Zhao, 2004; Miyake, Friedman, Rettinger, Shah, & Hegarty, 2001; Vandierendonck, Kemps, Fastame, & Szmalec, 2004). For example, Hamilton et al. (2003) found that an interpolated secondary (executive) task during the retention interval of a computerised CBT derivative significantly reduced task performance, providing evidence that the tasks involved common cognitive, in this case executive, resources. Furthermore, Miyake and colleagues (2001) employed statistical partialling techniques to examine the relationship between putative measures of VSWM, executive function, and spatial abilities, and found that conventional span procedures such as the CBT implicate executive functioning. These findings indicate that the CBT performance may demand executive resources, therefore variability in these resources would contribute to variability in performance. Euthymic bipolar patients’ performance deficit on the CBT could thus be due to their compromised executive function rather than their having impaired visuospatial memory per se. In order to identify precisely where within the VSWM functional architecture the deficit lies, this study employs a range of tasks (discussed below) chosen to make demands on visual, spatial, and executive processes in VSWM. The first of these measures, the Visual Patterns Task (VPT), was developed to measure the visual (as opposed to the spatial) component of VSWM (Della Sala, Gray, Baddeley, & Wilson, 1997). In this test, the subject is required to reproduce

EXECUTIVE /VISUOSPATIAL RESOURCES IN EBD

matrix patterns containing sets of similar elements in varying arrangements in the frontoparallel plane, eliminating the spatio-sequential component inherent in the CBT. While Della Sala, Gray, Baddeley, Allamano, and Wilson (1999) have provided evidence that the VPT is a purer measure of visual WM than the CBT, results from Hamilton and colleagues’ (2003) selective interference study suggest that this measure may also make demands on executive resources. Moreover, Miyake et al. (2001) found that recall performance of a similar matrix pattern test was strongly correlated with executive performance. Furthermore, Phillips and Hamilton (2001) observed an age-dependent inverted U-shape profile on a computerised variant of the VPT, with peak performance in young adults and poorer performance in children and elderly participants. This age trajectory is indicative of the development of executive processes in working memory (Baddeley, 1986; Phillips & Hamilton, 2001; Hamilton et al., 2003). The Size Just Noticeable Difference (JND) task has been explicitly developed to reduce its demands on executive resources (Phillips & Hamilton, 2001). Unlike the VPT, the developmental trajectory associated with this procedure is more typical of slave system function (Gathercole, 1999; Phillips & Hamilton, 2001). In addition, a protocol of this task has been previously adopted as an exclusively visual task, susceptible to dynamic visual noise (McConnell & Quinn, 2004). In the Size JND task the participant has to decide whether a stimulus presented in the encoding phase is the same size, or not, as a stimulus presented in the recognition phase, where these two events are interpolated with a retention interval. The participant is required to maintain a fine-grained representation of the size of the square in order to make a decision in the subsequent recognition phase. Difficulty is manipulated by successively reducing the percentage change in the size of the stimuli presented in the encoding phase and recognition phase in the ‘‘different size’’ trials. Participants who progress to the more difficult levels of these tasks are assumed to be capable of maintaining finer-grain visual representations than participants who fail to progress as far. The task therefore assesses the functional efficacy of visual working memory, i.e., it assesses how well one can represent material over time, as opposed to how much visual information is retained (i.e., complexity). In this sense it is more similar to other tasks in WM research such as the hue-discrimination task of

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Logie and Marchetti (1991), and the line-length procedure of Baddeley, Cocchini, Della Sala, Logie, and Spinnler (1999). This study also employed an index of the phonological loop (digits forwards) and two executive procedures (digits backwards and the Self-Ordered Pointing Task). Forward digit span requires the individual to store and reproduce a digit sequence in its correct serial order, where the number of digits to be remembered is progressively increased over successive trials. Within the working memory tradition, this task is commonly employed to assess phonological loop capacity (Baddeley, 1986; Gathercole, 1999). In the backward digit span procedure, the participant is required to recall a digit sequence in the reverse order of presentation. This task requires both storage (phonological loop) and transformation (processing) of material within working memory (Baddeley & Logie, 1999; Gathercole, 1998). Nonetheless, as with its forwards counterpart where the phonological loop is concerned, this measure has been extensively employed in the working memory literature to index central executive resources (e.g. Gathercole, 1998; Gathercole & Pickering, 2000). Moreover, using a correlational approach, Groeger, Field, and Hammond (1999) have demonstrated that digits backwards recruits executive resources. The utility of this measure as an index of executive function has also been observed within a clinical context in affective disorder populations (Channon, Baker, & Robertson, 1993; Ferrier, Chowdury, Thompson, Watson, & Young, 2004). The Self-Ordered Pointing Task (SOPT) is designed to measure the planning and monitoring functions of working memory (Petrides & Milner, 1982) and has been extensively used in a clinical context as an index of executive function (Pukrop et al., 2003; Rich, Bylsma, & Brandt, 1996; Shimamura & Jurica 1994; West, Winocur, Ergis, & Saint-Cyr, 1998). In the original task variant, a set of design stimulus items is arranged in different spatial locations on multiple pages, and participants are required to point to a different item on each page. The random location of designs across pages negates the use of a spatial strategy to facilitate task performance (Curtis, Zald, & Pardo, 2000). Like digits backwards, the SOPT makes demands on both storage and processing components of the working memory architecture (Rich et al., 1996). However, it may be distinguished from conventional span procedures such as the visual memory span subtest of

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the Wechsler Memory Scale Revised, in that it requires patients to plan, sequence, initiate, and monitor their own pointing responses, rather than follow a sequence dictated by the examiner (Spreen & Strauss, 1998). In addition to being supported by a rich clinical database, the SOPT has been reported to correlate with a number of well-established executive measures in a normative context (Daigneault & Braun, 1993). Moreover, Daigneault and Braun (1992) reported an age-related decline in SOPT performance, suggesting a profile more in accord with an executive, rather than a slave system developmental trajectory. We hypothesised that euthymic bipolar patients would be intact on the Size JND task. Given our previous finding of a persistent deficit in executive control, we further hypothesised that they would be impaired on executive measures, and on the conventional measures of VSWM (CBT & VPT). These predictions are derived from the series of independent empirical studies discussed above. However, this paper comprises a preliminary normative study whose aim is to further substantiate the clinical predictions and demonstrate the concurrent validity of the Size JND vis a` vis the VPT measure. In addition, the relationships of the visual and spatial memory measures with executive resources will be examined within the same study. The clinical study, where the aim is to identify which components of the VSWM architecture are selectively impaired in the patient group, will also explicate the implications this has for VSWM functional architecture.

YOUNG ADULT NORMATIVE STUDY: METHOD Participants A total of 82 young adults participated in the normative component of the research; 46 women and 36 men. The average age for the sample was 17.1 (0.71) years.

Procedure All of the participants completed all of the tasks within two sessions of approximately 45 minutes each. The order of the spatial executive task procedures was counterbalanced.

Cognitive tasks The Corsi Block Task (Milner, 1971); Visual Patterns Test (Della Sala et al., 1997). Size JND paradigm: In this task (Phillips & Hamilton, 2001), a single square stimulus was presented to participants for 2 seconds and, following a 4-second interpolated retention interval, a second square of either the same or a different size was presented in an offset position. The participant’s task was to state whether the second square was the same size as the initial square or a different size. The offset spatial location and size (in pixels) of the to-be-remembered stimulus was varied randomly across trials to ensure that the task involved the temporary representation of the square size rather than the construction of a long-term template of the square size. A maximum of 20 trials were carried out at each level, and the criterion for progression was 15/20 (binomial p B/.05) to counter the .5 probability for guessing. There were six levels that participants could progress through, where the percentage change in the size of the square was successively reduced, beginning at the entry level, a 50% change, through to the most difficult level, a 6% change in stimulus size. The participant’s score was the most difficult level at which the criterion was satisfied, e.g., 50%, 40%, 30%, 20%, 10%, or 6%. Note that with this scoring system, a lower value indicates a better visual memory performance. Two spatial executive tasks were additionally employed here to assess visuospatial executive competency. These task protocols are frequently employed in a normative context (Kane, Hambrick, Tuholski, Wilhelm, Payne, & Engle, 2004; Miyake et al., 2001; Shah & Miyake, 1996). The Letter Spatial Executive Task has two components; the mental rotation element (MRT) where participants had to judge whether two letters of different orientations were the same or mirror images of one another, and the concurrent maintenance of location, where for each MRT participants had to remember the spatial location of the top of letter on the right of the screen. This procedure mimicked the Shah and Miyake protocol, apart from one feature in the present procedure where a small red spot was added to the top of the letter in order to facilitate the precise spatial location of the top of the letter. Prior to the task beginning, participants received practice on each of the two components of the task individually.


Participants then began with the judgement of one pair of letters and the identification of the one spatial location. Progression to two MRT judgements and recall of two locations (in appearance order) depended on successful completion at Level One (one judgement) of three out of five trials undertaken. Successful completion at Level Two (two MRT judgements and two sequential recall of locations) enabled the participant to progress to the next level with three judgements and spatial locations, and so forth. In the Block Spatial Executive Task , the 2-D mental rotation of letters employed in the task above was replaced by mental rotation of ‘‘3-D’’ stimuli of block shapes. These stimuli were based on stimuli conventionally employed in the individual differences literature (Shepard & Metzler, 1971; Hamilton, 1995; McWilliams, Hamilton, & Muncer, 1997). The task protocol was identical to the Letter Spatial Executive task above, with the small red spot attached to the top of the block stimulus on the right of the screen. Span for both executive variants was defined as the highest level that the subject successfully recalled at least three trials at that level. Successful trials beyond three at that level or up to two at the next level were also integrated into the span score.

YOUNG ADULT NORMATIVE STUDY: RESULTS Table 1 indicates the descriptive statistics for the young adult task performances. Note that the change in processing task from 2-D letter rotation to 3-D block rotation significantly impaired executive span performance, F (1, 80) /27.86, p B/ .001. In Table 2, the bivariate correlations between the measures are displayed. An additional measure, the factorial extraction of Letter Spatial Executive and Block Spatial Executive, is also included. The use of this measure reduces the possibility that the observed relationships are a result of features specific to the individual tasks. This table provides support for the suggestion that both the VPT and Corsi tasks procedures make demands on executive resources. Both tasks are significantly correlated with the executive factor. Note also that the Size JND mnemonic task does not correlate with the executive factor but does display a significant correlation with the VPT task. This suggests that the VPT procedure makes demands of both an executive nature and visual maintenance nature. To investigate these findings further, a hierarchical regression was carried out with VPT as the criterion and Size JND and the Executive Factor measures as the predictors. The analysis revealed that the Size JND task added 5.8% of unique variance, F (1, 89) / 5.65, p / .020, while the Executive Factor added 10% of unique variance, F (1, 89) / 9.933, p/.002. These results suggest that visual maintenance, as measured by the Size JND task, and executive resources, as indexed by the Executive factor, are both significant but also unique contributors to the variance in VPT task performance. This pattern of results indicates that while the Size JND task acts as a valid measure of visual

TABLE 1 Mean task performance for young adult normative sample Task

VPT

Size JND

Corsi Blocks

Letter Spatial Executive

Block Spatial Executive

9.25 (1.53)

15% (7.35)

5.78 (0.85)

2.26 (0.62)

1.9 (0.72)

Data are given as mean (SD ). VPT /Visual Patterns Test; Size JND/Size Just Noticeable Difference paradigm.

TABLE 2 Intercorrelations between tasks for young adult normative sample

Task Size JND Corsi Blocks Letter Spatial Executive Block Spatial Executive Executive Factor

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VPT

Size JND

Corsi Blocks

Letter Spatial Executive

Block Spatial Executive

/0.30** 0.44*** 0.31** 0.33** 0.37***

/ /0.18 /0.20 /0.11 /0.18

/ 0.15 0.33** 0.27**

/ 0.56*** 0.88***

/ 0.88***

Young adults (n/82). VPT/Visual Patterns Test; Size JND/Size Just Noticeable Difference paradigm. *p B/.05. **p B/.01. ***p B/.001.

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memory processes in VSWM, it is less dependent on visuospatial executive resources. The relationships evident in this data set between the VPT, Corsi, and Visual JND are therefore entirely consistent with the evidence discussed above.

CLINICAL STUDY: METHOD Participants A total of 20 Caucasian patients with DSM-IV confirmed Bipolar Affective Disorder (17N BPI; 3N BPII) were recruited from north-east England. All patients were stabilised on prophylactic medication at test. Eleven were taking more than one drug (see Appendix Table A1). Patients were excluded if they were taking corticosteroids or antihypertensive medication, had any other current axis I diagnosis, had a neurological or medical condition, had any history of substance or alcohol misuse in the past 6 months, or if ECT had been administered in the past year. A total of 20 (DSM-IV screened) physically healthy volunteers were recruited from the community by advertisement. Controls were matched on an individual basis with patients for age (9/5yrs), sex, handedness (Briggs & Nebes, 1975), years of education (9/3yrs), and premorbid IQ (NART9/5 IQ points, Nelson, 1982). Controls were excluded if they had any history of psychiatric disorder, had a family history of affective disorders in a first-degree relative, or were currently receiving medication (except the oral contraceptive pill). Table A1 in the Appendix provides a summary of the participants’ demographic and clinical characteristics. After complete description of the study to the participants, written informed consent was obtained. The local Ethics Committee approved the investigation.

Newcastle euthymic protocol Residual mood symptoms have been found to impact on cognition in affective disorders (Ferrier et al., 1999), therefore we have designed and validated (Thompson et al., 2000, 2005) a rigorous euthymic protocol to eliminate this confound. Following referral from their clinician, patients were prospectively verified as euthymic over 1

month prior to test. Euthymia was defined as scores of 5/7 on the Hamilton Depression Rating Scale (Hamilton, 1960) and the Young Mania Rating Scale (Young, Biggs, Ziegler, & Meyer, 1978) at initial assessment and after 1 month. Patients also completed weekly Beck Depression Inventory (BDI, Beck & Ward, 1961) and Altman Mania Rating Scales (AMRS, Altman, Hedeker, Peterson, & Davis, 1997) during the euthymic verification month. Controls completed the same clinical ratings as patients on the study day following a pre-screen AMRS and BDI 1 week prior to test (see Appendix Table A1).

Ratings DSM-IV diagnoses were established by trained psychiatrists using the Structured Clinical Interview for DSM-IV-Patient Version (SCID-I/P, Version 2.0). Controls were interviewed with the non-patient edition (SCID-I/NP). Illness characteristic data (Appendix Table A1) were derived from retrospective life charts constructed from patient interview and hospital medical records (Leverich & Post, 1996). All participants completed the Alcohol Use Disorders Identification Test (AUDIT, Babor de la Fuente, Saunders, & Grant, 1992) to exclude current alcohol misuse. History of and current substance use were assessed via DSM-IV criteria and a detailed inventory derived from the major DSM-IV substance classifications. This self-report instrument was used to exclude participants who had used unprescribed substances over the last 6 months, and to ascertain any prior use. The MiniMental State Examination (Folstein, Folstein, & McHugh, 1975) was administered to screen for dementia.

Cognitive tasks Cognitive testing commenced at 2 pm on the study day. All tasks were administered by a trained psychology graduate and took 2 hours to complete. The order of tasks remained invariant across participants. Detailed descriptions of all measures are provided below. Phonological loop task. Forward digit span: Verbal WM capacity was assessed via the digits forward task from the Wechsler Adult Intelligence Scale Revised


(WAIS-R, Wechsler, 1981). In this test, the participant attempts to verbally reproduce a random sequence of digits, presented at the rate of one per second, in their correct serial order. The difficulty level is progressively raised by increasing the number of digits in the sequence. There are two trials at each difficulty level and progression through the series requires that participants succeed on at least one trial at a particular level. Span was defined as the highest level that the subject recalled at least one sequence of stimuli in their correct serial order (maximum /9). Spatial working memory task (CBT). Spatial span test: Spatial WM capacity was assessed with a computerised version of the Corsi Blocks Test (CANTAB). This task was presented on a 486 microcomputer fitted with a high-resolution 15-inch MicroTouch touchscreen monitor. Participants were seated 0.5 m from the monitor and were instructed to respond to stimuli in each task by touching the screen. In this test, the participant attempts to reproduce a sequence of stimuli locations in their correct serial order. Stimuli are presented randomly at the rate of one stimulus per second with a 3-second delay prior to the recall phase. The sequences are random and the difficulty level is progressively raised by increasing the number of stimuli in each sequence. There are three trials at each level and progression requires participants to succeed on at least one of these trials. Whenever a trial is correctly completed, the computer automatically administers the next level. Span was defined as the highest level that the subject successfully recalled at least one sequence of stimuli in the correct serial order (maximum /9).

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Self-Ordered Pointing Task (Petrides & Milner, 1982): A computerised version of this task was operationalised using Sens 1.7 software (tornadolabs), where participants were presented with an array of abstract designs on a touchscreen monitor arranged in a hidden 3 /4 grid. The goal of the task was to select each design only once in any order. After each touch, the designs were randomly reordered in the matrix, thus eliminating spatial cues. Three trials were given at each set size of 4, 6, 8, and 10 designs. The same designs were used repeatedly within a set and different designs were used across set sizes. Participants responded by touching each chosen design via the touchscreen monitor with their dominant hand. Each trial terminated once the subject has performed a number of touches, corresponding to the set size at that level. The task was self-paced and no feedback was given. An error was recorded each time a participant selected a pattern that was chosen previously. The total number of errors across all levels constituted the score.

CLINICAL STUDY: RESULTS Demographic and mood data There were no significant between-group differences across the demographic variables. Furthermore, patients exhibited few residual mood symptoms on the clinical rating scales across the euthymic verification period, and their scores were no different from control participants when both groups completed these ratings (see Table A1 in Appendix).

Cognitive measures Visual memory tasks Visual Patterns Test (Della Sala et al., 1997). Size JND task: This protocol was described above in the Methods section of the young adult study. Central executive measures. Backward digit span (Wechsler, 1981): The administration and scoring procedures for this task are the same as the forward sub-test, except that participants have to reproduce the digit sequences in reverse order (maximum possible score /8).

The pattern of bivariate correlations in the main clinical study is shown in Table 3. A striking similarity with the normative data is evident. The Size JND was significantly correlated with the VPT but with neither of the executive measures. This independent observation again indicates the contribution of the Size JND performance to VPT variance. Again, the VPT was correlated with the executive factor. The visual maintenance measure (Size JND) contributed significant unique variance to VPT performance, F(1, 37) /17.566, p B/.001. The executive factor measure also contributed unique variance,

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TABLE 3 Intercorrelations between tasks for the (pooled) sample within the clinical study

Tasks

VPT

Size JND /0.50*** Corsi 0.46** Blocks Backward 0.53*** Digit Span SOPT /0.47** Executive 0.59*** Factor

Size JND

Corsi Blocks

/ /0.17

/

/0.09

0.51***

Backward Digit Span

SOPT

/

/0.03 /0.46** /0.45** / /0.07 0.57*** 0.85*** 0.85***

Patient/Control sample (n /40). VPT/Visual Patterns Test; Size JND/Size Just Noticeable Difference paradigm; SOPT/Self-Ordered Pointing Task. *p B/.05. **p B/.01. ***p B/.001.

F (1, 37) /25.454, p B/.001. This pattern mimics the young adult pattern identified above. The CBT was correlated with the two executive measures (Digits Backwards and the SelfOrdered Pointing Task) and the factor extracted from these two measures. Yet the digits backwards task is verbal in nature, sharing little in its protocol with the CBT procedure. Again this relationship between the CBT and executive resources is consistent with the arguments considered above and that observed in the normative study, supporting the evidence for a close relationship between the CBT and executive resources.

Group mean performance and statistical comparisons (via independent t -tests) for each cognitive measure (organised by domain) are summarised in Table 4. Patients were significantly impaired on both of the executive measures employed, recalling fewer digits than controls on the Backward Digit Span Test, and making significantly more errors on the SOPT. In addition, patients’ spatial span, as indexed by the CBT, was significantly lower than the control group. Contrary to the performance deficit observed on the Backward Digit Span Test, there was no between-group difference in the number of digits recalled on the Digits Forward task. Patients were also intact on both of the visual memory procedures, the VPT and Size JND task.

Executive dysfunction as a predictor of between-group variance on the CBT Evidence from previous selective interference studies (Hamilton et al., 2003; Vandierendonck et al., 2004) and the bivariate correlation data in the present two studies suggest that the CBT makes extensive demands on executive resources. As the between-group comparisons illustrate that bipolar patients have a deficit in executive control, their performance deficit on the CBT may therefore be mediated by their compromised executive function. In order to provide a direct assessment of this, Analysis of Covariance (ANCOVA) was used. If patients’ deficit on the CBT is indeed mediated by executive task

TABLE 4 Between-group cognitive performance comparisons in the clinical study Measure Phonological loop Forward digit span

Bipolar (n /20)

Controls (n /20)

t value

p

95% C.I. of the difference

6.80 (1.40)

7.15 (1.39)

0.794

.43

/0.54 to 1.24

Visuospatial sketchpad Spatial span c (Corsi Task) Pattern span (VPT) c Size JND paradigm b

4.95 (1.50) 8.30 (2.47) 14.00 (8.46)

6.00 (0.97) 8.85 (1.23) 12.10 (4.83)

2.662** 0.891 /0.872

.01 .38 .39

0.24 to 1.86 /0.71 to 1.81 /6.32 to 2.52

Central executive Backward digit span SOPT total errors a, b

4.40 (1.54) 14.60 (5.95)

5.50 (1.40) 9.30 (5.54)

2.371* /2.916**

.02 .01

0.16 to 2.03 /8.98 to /1.62

Data are given as mean (SD ). SOPT/Self-Ordered Pointing Task; VPT /Visual Patterns Test; Size JND/Size Just Noticeable Difference paradigm. a As there is more than one level of difficulty for this task, the mean score collapsed across levels or stages is reported. b The lower the score on these measures, the better the performance. c These tasks putatively tap the resources of both the visuospatial sketchpad and the central executive, although results from these tasks are reported only once in the table for the sake of parsimony. *p B/.05. **p B/.01.


performance, then one would expect the previously demonstrated between-group difference on the CBT to disappear once the executive contribution was partialled out. In the first ANCOVA model, SOPT performance was entered as a covariate, group membership (BPD vs controls) was entered as the between subjects (fixed) factor, and Corsi Blocks performance was entered as the dependent variable. This analysis illustrated that SOPT (the covariate) had a significant effect on CBT performance; F (1, 37) /5.239, p /.028. Furthermore, the previously observed between-group difference in CBT performance (main effect of group) did disappear once the SOPT executive contribution to performance was partialled out; F (1, 37) / 2.310, p /.137. A second ANCOVA was subsequently conducted to ascertain whether the executive contribution to Corsi Blocks performance is generic in nature, rather than being domain specific. In this analysis, the (predominantly visuospatial) SOPT variable was replaced by the verbal executive measure (backward digit span). All other variables remained invariant. Again, the covariate (executive measure) had a significant effect on CBT performance; F(1, 37) /8.419, p / .006, and the between-group difference in CBT performance was no longer significant once the backward digit executive contribution to performance was controlled; F(1, 37) /2.669, p /.111. The third ANCOVA employed the extracted executive factor as the covariate and found that the executive factor covariate had a significant effect on CBT performance, F(1, 37) /13.819, p /.002. The group difference in CBT performance was not significant, F (1, 37) /1.189, p /.283. This final analysis illustrates that it is the common executive resources between these two quite disparate procedures that contribute to the CBT group effect, and strengthens the case for executive resource constraints as opposed to spatial short-term memory per se, in euthymic bipolar disorder. The suggestion from these analyses is that the patient difficulty with the Corsi procedure is a result of impaired executive contributions to task performance. However, one could raise the question of why the VPT, which was also correlated with executive resource measures (in both studies) was not similarly affected. One possible explanation is that the VPT requires distinct, visual memory processing (Della Sala et al., 1997) and the

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present results, in both studies, suggest that visual maintenance performance contributes to VPT variance and thus could scaffold performance in the face of impaired executive contribution.

DISCUSSION The aim of this study was to investigate the nature of working memory functional architecture in patients with euthymic bipolar disorder. It was hoped that the articulation of the pattern of deficits and competencies would shed light on the nature of the slave system /executive interface within a normative context. The preliminary study sought to establish the relationship between visuospatial working memory tasks and executive resources within a normative sample of young adults. These results provided further evidence that conventional VSWM tasks such as the Corsi Blocks task and Visual Patterns task share common variance with executive task performance. In addition, the preliminary study indicated that the Size JND task performance correlates with the VPT while showing no significant correlation with the executive measures. The pattern of correlations observed in the preliminary study was replicated in the clinical component of the research. Initial analyses indicated that the patient group was impaired in spatial span, and the two executive measures; the Self-Ordered Pointing task and the backward digit span. Specifically, patients committed more pointing errors than controls on the SOPT and their backward digit span was significantly lower than controls. Both of these tasks place high demands on the capacity to monitor and manipulate cognitive representations online, suggesting that patients’ deficit resides in their ability to monitor the contents of WM. These findings are consistent with the research discussed in the Introduction, which independently identified executive and spatial memory (Corsi) task deficits in bipolar patients (Ferrier et al., 1999; Thompson et al., 2000). In contrast, the results also suggest that VPT performance was not compromised in the patient group. This competency occurred despite the strong correlation between the VPT performance and executive task performance. In addition, there was no impairment in the patient group in the Size JND task performance. The present study, by considering performance on a range of VSWM and executive tasks, was

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able to consider the contribution of executive resources to spatial span competency. Three separate ANCOVA procedures controlled for executive task performance when comparing spatial span performance between the patient group and the matched control group. In all three analyses, the group comparison was no longer statistically different. This consistent pattern suggests the patient group deficit in spatial span performance is not the result of a deficit in spatial memory per se, rather it is a consequence of impaired executive resources which would typically scaffold or support performance in the spatial span task. This interpretation is consistent with Bearden et al. (2001) who, in their review of cognitive function in bipolar illness, concluded that visuospatial deficits are more reliably indicated on complex tasks that comprise components other than their spatial requirements. This impairment cannot be attributed to residual mood symptoms in our patient sample (Ferrier et al., 1999) as between-group differences in mood were excluded by the stringent euthymic protocol employed in this study. However, patients with varying medication regimes were included in this study and the size of the patient group was too small to investigate the possible influence of different prophylactic treatment strategies. We cannot therefore exclude the possibility that medication effects may partly explain our results. However, it is unlikely that medication alone could account for the specific impairment observed in this sample, as abnormalities on executive paradigms reported by our own group and others have been confirmed in a cohort of bipolar patients who had been drug free for at least 6 months (Goswami et al., 2001). The results illustrate the importance of using methods derived from an empirically defined model of cognitive architecture to guide investigations of the deficits involved in bipolar disorder. This rigorous approach, taking advantage of cognitive theory, allows a more comprehensive delineation of the apparent deficits. Yet, where cognitive theory and associated methods will provide a framework from which to derive, in a principled manner, profitable investigation, interpretation will be hindered whenever the methods do not target the cognitive components specified. One specific role of any theoretical framework is to provide well-understood tasks for collecting data. In keeping with other investigations, including those using an individual differences approach (Miyake et al., 2001), our results indicate that

several of the tasks traditionally used to specify the slave systems of WM may be failing to exclusively target these systems. In particular, the CBT may reflect executive components more than any putative spatial component. Whether the executive involvement in these tasks involves a strategic maintenance processes (Shah & Miyake, 1996) or simple refresh maintenance (Baddeley et al., 1999) is beyond the scope of this article, as is the exact nature of the visual memory contribution to the VPT. None the less, caution is required when assuming that tasks are making exclusive demands on any one component of the architecture. Indeed, any cognitively demanding task is likely to involve more than one component of WM and the experimentally tractable nature of the CBT and VPT may belie their complexity. These results have clear implications for studies employing the selective interference procedure, as any uncertainty in the processes targeted by either the primary or the secondary interference task may lead to uncertain or confounded conclusions about the locus of interference. An overriding issue in the literature is whether the overlap in cognitive demands observed in concurrent dual task studies reflects the operation of a specialised visuospatial component of WM or more general-purpose attentional resources. In so far as we accept that digits backwards and the SOPT are tasks that tax such general resources, our data are clear. Both the CBT and VPT rely heavily, though differentially, on some common resource. Consequently, evidence that performance on the two tasks can be dissociated need not necessarily reflect the visual and spatial nature of the tasks. It may be their differential demand on executive support that is critical to differences in performance in the patient group. In view of our results, it would be interesting to explore further the extent to which visual, spatial, or general-purpose resources are involved in the retention of putative visual or spatial material. However, to disentangle the effects of general and more specialised cognitive resources, future studies should routinely include executive procedures in their interference armoury. This seems particularly warranted considering that executive resources have also been implicated in spatial tapping, the flagship secondary interference task for the visuospatial sketchpad (Morris, 1987). A similar critique could be levelled at developmental studies, which indicate that the VPT


and CBT have distinct developmental trajectories (Logie & Pearson, 1997). Logie and Pearson interpret this pattern as supporting the fractionation of VSWM into distinct visual cache and inner scribe components. However, a differential demand on executive and visuospatial support across the VPT and CBT as evidenced in our study suggests that a reconsideration of this view is merited. Currently, the observed pattern cannot discriminate between a pattern resulting from changes in the sub-components themselves as opposed to a pattern emerging from the change in the functional interactions between these slave processes and other components of the VSWM architecture (Hamilton et al., 2003). As the extent to which separable cognitive structures can be genuinely isolated (and measured) by any visuospatial measure is in question, the extent to which neuropsychological cases can be viewed as a ‘‘visual’’ patient or a ‘‘spatial’’ patient is also compounded (Pickering, 2001). Any putative visuospatial impairment may be secondary to a defect in the central executive (e.g., Grossi, Becker, Smith, & Trojano, 1993). This situation is further complicated given that our results suggest that patients are able to sustain their performance on particular tasks if preserved processes contribute to task performance, irrespective of whether these tasks also draw on resources that are impaired. (It will be recalled that patients’ performance was preserved on the Visual Patterns Test, which made demands on both visual and executive resources.) Clearly, until we have a better understanding of the processes involved in dissociable tasks, we cannot be sure about the nature of the fractionation of VSWM, or our interpretations regarding the integrity of this architecture in an applied setting. Several authors have observed that the study of VSWM has been hindered by the lack of suitable procedures to assess the architecture (e.g. Baddeley, 1998). The Size JND task seems to yield promise here given that it correlated with the VPT task but showed no relationship with the executive measures employed in this study. This procedure was explicitly designed using a componential approach (Farah, 1984) to preclude the use of alternative (executively controlled) strategies during the maintenance of visual information. It was assumed that the use of a simple, single stimulus would reduce the requirement for a complex representation, thus minimising the need for scanning or chunking strategies that may be employed in the conventional visual task

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(VPT), an assumption that seems to have been borne out (Klauer & Zhao, 2004). The huediscrimination task of Logie and Marchetti (1991), the line-length procedure used by Baddeley and colleagues (Baddeley et al., 1999), and the use of dynamic visual noise (Quinn & McConnell, 1996), also appear to be good examples of protocols requiring less strategic rehearsal. Thus, further exploration of VSWM architecture using these procedures could prove extremely profitable. While the feedback from cognitive theory to investigations of affective disorder is clear and welcome, the feed-forward benefits are thus also clear, not only in the analyses of the tasks, but also in the contribution to the architecture. A particularly compelling aspect of our results is that they accord with those of Miyake et al. (2001), who draw a particularly close association between visuospatial task and executive processes. Indeed, Miyake et al. highlight the strong relationship between executive processes and visuospatial memory tasks whether or not the latter heavily involve spatial processes, as in the CBT, or more visual processes, as in their dot matrix recall task (aka VPT). These authors do acknowledge evidence for a short-term visual storage system that maintains a simple representation, requiring no transformation, although a distinct storage system was not evident in their analyses of the conventional span procedures. Our results suggest that processes involved in the recall of the dot matrix or visual pattern type of task include executive processes and are in this regard consistent with Miyake et al.’s results. However, we have also provided evidence, through the relationship of the Size JND and the VPT, that such tasks may involve a separate and functional visual component (Della Sala et al., 1997). In conclusion, a fuller understanding of the VSWM architecture not only requires a clearer picture of the nature and functions of the central executive system and its relationship to the visuospatial sketchpad, but also further consideration of task demands. The results provided here indicate that the visuospatial architecture should reflect the closeness of visuospatial and executive processes, rather than reflecting a symmetry between verbal and visual short term processes (Logie, 1986). Manuscript received 26 June 2003 Manuscript accepted 8 November 2005

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APPENDIX TABLE A1 Demographic and clinical characteristics in the clinical study Variable Demographic characteristics Age, years Number of participants, female:male Education, years Premorbid IQ (NART) Handedness, Number of right:left:mixed Mood ratings HAM-D (initial assessment) YMRS (initial assessment) BDI Week 1 BDI Week 2 BDI Week 3 BDI Week 4 a AMRS Week 1 AMRS Week 2 AMRS Week 3 AMRS Week 4 HAM-D (post-month assessment) YMRS (post month assessment) a

a

Clinical characteristics Age at illness onset, years Duration of illness, years Number of hospital admissions Number of depressed episodes Lifetime months of depression Number of manic episodes Lifetime months of mania Mood stabilisers Antidepressants Anticholinergics Benzodiazepines Antipsychotics, typical:atypical Dose (mg/day) chlorpromazine equivalent b No. of previous ECT treatments (n /8) Time since last ECT treatment, years (n/8)

Bipolar (n/20)

Controls (n/20)

p

45.60 (9.23) 10:10 14.15 (3.36) 107.15 (10.00) 18:0:2

45.95 (9.41) 10:10 14.98 (2.97) 107.25 (11.20) 19:0:1

.91 1.0 .42 .98 /

1.90 1.40 2.10 2.80 2.55 1.85 2.50 1.45 1.55 1.40 1.40 0.65

(2.38) (2.08) (2.27) (4.32) (3.20) (3.18) (2.89) (1.67) (1.70) (1.73) (2.30) (1.46)

26.15 (7.69) 19.95 (10.47) 3.15 (3.33) 12.85 (17.58) 21.42 (20.95) 11.40 (21.60) 12.92 (27.25) 19 5 0 1 2:3 144.33 (50.95) 6.43 (4.39) 19.29 (4.27)

/ / / / / 1.05 / / / 2.20 0.40 0.20 / / / / / / / / / / / / / / /

/ / / / / (1.67)

.90 / / /

(2.89) (0.75) (0.41)

.55 .36 .64 / / / / / / / / / / / / / / /

All data given as the mean (SD ). IQ/Intelligence Quotient; NART /National Adult Reading Test; HAM-D/Hamilton Depression Rating Scale; YMRS/ Young Mania Rating Scale; BDI/Beck Depression Inventory; AMRS/Altman Mania Rating Scale; ECT/Electroconvulsive Therapy. a Shapiro-Wilks and Levene’s tests confirmed that these variables did not meet the assumptions of normality and homogeneity of variance respectively. Between-group comparisons were therefore conducted via the non-parametric Mann-Whitney U test. All other (demographic, mood, and cognitive) variables fulfilled the assumptions of parametric testing and were therefore analysed using independent samples t -tests. b See Rey et al. (1989) for details.