Elsevier

Psychiatry Research

Volume 179, Issue 3, 30 October 2010, Pages 253-258
Psychiatry Research

Impaired spatial working memory maintenance in schizophrenia involves both spatial coordinates and spatial reference frames

https://doi.org/10.1016/j.psychres.2009.09.002Get rights and content

Abstract

Spatial working memory (SWM) dysfunction is a central finding in schizophrenia; however, more evidence of impaired maintenance over time is required. Consequently, the present study examined SWM maintenance over short unfilled delays, and with encoding equated. The influence of a vertical reference frame to support maintenance was also investigated. The performance of 58 patients with schizophrenia and 50 healthy controls was assessed using the Visuo-Spatial Working Memory (VSWM) Test across three unfilled delays (0, 2, and 4 s). Inaccuracy of direction and distance responses was examined at each delay duration. The results showed that performance was significantly less accurate for both distance and direction responses at 2 and 4 s delays in schizophrenia, but was not significantly different from controls at the 0 s delay. Patients showed a particularly marked loss of accuracy between the time interval of 0–2 s. Furthermore, schizophrenia participants exhibited significantly greater response variability at the vertical axis of symmetry than controls at the 2 and 4 s delays, but not at the 0 s delay. These data clearly show both impaired maintenance over time and difficulty using a vertical frame of reference in schizophrenia. The latter findings may reflect, in part, dysfunctional reference-related inhibition.

Introduction

The centrality of working memory (WM) deficits in individuals with schizophrenia (Lee and Park, 2005, Piskulic et al., 2007, Forbes et al., 2008) has led the NIMH initiative Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) to select this cognitive domain as a target for translational research (Barch and Smith, 2008). This decision reflects, in part, the impact that impairments in WM have on social and occupational functioning (Green et al., 2000, Cervellione et al., 2007). Reflecting the multi-component nature of WM, the CNTRICS working party determined that the WM constructs of goal maintenance and interference control were ready for immediate application in clinical trials (Barch et al., 2009). In contrast, the construct of maintenance over time – that is, the ability to maintain target representations internally during a delay period (Park and Lee, 2002) – was recognized as having good construct validity but in need of more clinical research to determine whether this mechanism is impaired in schizophrenia (Barch and Smith, 2008).

At the neural level, recent evidence supports the notion of a time-dependent impairment during spatial working memory (SWM) maintenance in schizophrenia (Driesen et al., 2008). However, behavioral evidence concerning the effects of delay duration has been somewhat mixed. Early studies suggested that increasing the delay duration worsens the SWM deficit in patients with schizophrenia when compared to healthy controls. For example, using oculomotor and haptic delayed-response tasks, Park and Holzman (1992) showed that schizophrenia patients made more errors after a 30 s than after a 5 s delay and were thus vulnerable to increasing delay periods. Others have suggested that SWM deficits may be stable regardless of the length of delay (Keefe et al., 1995, Keefe et al., 1997, Leiderman and Strejilevich, 2004, Lee and Park, 2005). Importantly, based on a meta-analysis of 124 studies (of both spatial and verbal WM) Lee and Park (2005) reported that increasing the delay duration beyond 1 s did not influence the performance difference between controls and individuals with schizophrenia, indicating that encoding and/or the early part of maintenance may be particularly impaired.

Differences in task methodologies have also complicated the interpretation of these mixed findings. In particular, many studies of SWM have used filled-delays (i.e., distractors presented during the delay period) (Park and Holzman, 1992, Stratta et al., 1999, Hartman et al., 2002), consequently poor performance by individuals with schizophrenia may be due to difficulties with interference control rather than impaired maintenance over time (Turvey, 1973, Barch and Smith, 2008). In addition, many studies have measured SWM maintenance without controlling for differences in the initial encoding of visuospatial targets; again such studies cannot be unambiguously linked to an impairment in maintenance over time. However, both Tek et al., 2002, Badcock et al., 2008 did equate for encoding differences and found evidence of impaired maintenance of spatial information over relatively short (3 and 4 s, respectively) unfilled delays, supporting Lee and Park's (2005) proposal that the earliest part of maintenance is impaired in schizophrenia.

Basic research in spatial memory also highlights the importance of reference frames (i.e., category boundaries that divide space into smaller regions) in maintaining spatial representations over short and long delays (Huttenlocher et al., 1991, McNamara and Diwadkar, 1997, Spencer and Hund, 2002). While the precise spatial coordinates of visual targets decay rapidly after stimulus offset, perceived reference frames can support the accurate memory of spatial locations. For example, the dynamic field theory (DFT) of spatial cognition (Schutte et al., 2003, Spencer et al., 2007, Simmering et al., 2008) predicts that variance in WM responses near reference axes (e.g., the perceived vertical midline or symmetry axis of a target display) should be low compared to responses away from reference axes; and such predictions have been supported empirically in healthy adults (Spencer and Hund, 2002, Simmering et al., 2006), though such effects have received little attention in studies of schizophrenia.

In sum, there is a clear need for further studies examining whether maintenance over time in SWM is impaired in schizophrenia, using unfilled delays and with stimulus encoding equated (Barch and Smith, 2008). Furthermore, existing evidence suggests that maintenance over very short delays (1–2 s after stimulus offset) is of critical importance. In the current investigation, we used a modified delayed-response task, the Visuo-Spatial Working Memory (VSWM) test (Badcock et al., unpublished test), to examine this issue. The VSWM uses a staircase procedure to equate differences in the speed of encoding in working memory. Using this task, Badcock et al. (2008) showed that the performance of schizophrenia patients was equivalent to that of healthy controls at 0 s delay but less accurate compared to healthy controls at 4 s delay. The current study aimed to replicate and extend these findings, in an independent sample of individuals with schizophrenia and healthy controls, by including an intermediate delay period of 2 s. In addition, the VSWM task provides separate examination of direction and distance responses, which are distinct features of reaching movements (Gordon et al., 1994, Chieffi and Allport, 1997, Smyrnis et al., 2003), within a stimulus array that allows us to examine the variability of responses near to and away from the vertical midline axis. Consequently, the second aim of the current study was to examine whether individuals with schizophrenia are impaired in the use of a vertical reference frame, which normally supports the recall of spatial locations as delay increases. Finally, since poor SWM performance in schizophrenia may reflect general deficits in memory and attention, or side effects of (anticholinergic) medication, we also examined the influence of these variables on performance.

Section snippets

Participants

A group of 58 patients (46 males) was recruited through consecutive admissions to a psychiatric hospital. All patients met both International Classification of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for a lifetime diagnosis of schizophrenia or schizophrenia spectrum disorder. At the time of testing, patients were taking their usual medication, n = 50 atypical antipsychotics, n = 2 typical antipsychotics, n = 6 on both, n = 7

Results

Table 1 presents the demographic and clinical information and results on the cognitive measures for the participants. The groups were well matched for age, gender, and hand preference, but patients had completed fewer years of education than control participants. Current and premorbid IQ was significantly higher in controls than in patients; controls had significantly higher scores on immediate and delayed recall of RAVLT, and better performance (higher sensitivity/faster reaction time) on the

Discussion

While evidence has been accumulating to show that individuals with schizophrenia exhibit dysfunctional SWM, the precise mechanisms involved have remained unclear (Barch and Smith, 2008). The primary aim of the current study was to examine SWM maintenance over short delays (0, 2, and 4 s) in the absence of distractors and with encoding equated in order to examine whether the very earliest part of maintenance is impaired in schizophrenia. The secondary aim of this study was to investigate whether

Acknowledgments

This project was conducted within the framework of the Western Australian Family Study of Schizophrenia, funded by grants #404046 and #513874 from the National Health and Medical Research Council of Australia (NHMRC), with additional contributions from the North Metropolitan Area Health Services (NMAHS) in Perth, Western Australia. The first author was supported by an International Postgraduate Research Scholarship (IPRS) award from The University of Western Australia (UWA). SM and JCB

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