Elsevier

Schizophrenia Research

Volume 38, Issue 1, 27 July 1999, Pages 37-50
Schizophrenia Research

Neuropsychological and oculomotor correlates of spatial working memory performance in schizophrenia patients and controls

https://doi.org/10.1016/S0920-9964(98)00178-9Get rights and content

Abstract

Recent reports of spatial working memory deficits in schizophrenia provide evidence for dorsolateral prefrontal cortical (DLPFC) dysfunction. However, the question of how spatial working memory performance relates to other task impairments in schizophrenia considered reflective of frontal dysfunction, such as the Wisconsin Card Sorting Test (WCST) and smooth pursuit eye tracking, has been largely unexplored. Spatial working memory, as measured by a computerized visual–manual delayed response task (DRT), was evaluated in 42 schizophrenia patients and 54 normal controls. Subjects also completed a battery of neuropsychological and oculomotor tasks. Schizophrenia patients performed as accurately as controls on a no-delay, sensory–motor control condition, but showed a significant impairment in spatial accuracy with the addition of an 8-s delay and verbal distraction task. For the patients, working memory impairment was associated with fewer categories on the WCST, impaired eye tracking, fewer words learned on the Rey Auditory Verbal Learning Test, but not with measures of general cognitive and clinical functioning. Results suggest the presence of a sub-group of schizophrenia patients with common pathophysiology that accounts for the co-variance of several tasks implicating prefrontal dysfunction.

Introduction

The notion that the pathophysiology of schizophrenia involves frontal lobe dysfunction, an idea that dates back to Kraepelin (1971), continues to represent one of the prevailing neuroanatomical theories of schizophrenia. Support for the frontal lobe theory arises from multiple lines of evidence, including phenomenology (Seidman, 1983; Levin, 1984a), neuropsychological impairment (Goldberg and Weinberger, 1986; Goldsamt et al., 1993), oculomotor functioning (Levin, 1984b), and functional brain imaging (Buchsbaum et al., 1982; Weinberger et al., 1986). In particular, the pioneering series of rCBF activation studies by Weinberger and his colleagues using the Wisconsin Card Sorting Test (WCST) provided compelling evidence for physiological dysfunction of the prefrontal cortex in schizophrenia.

Recent reports of working memory deficits in schizophrenia provide the latest line of evidence for the frontal dysfunction hypothesis. The concept of `working memory' has its roots in cognitive psychology (Baddeley, 1986), referring to a memory system responsible for the temporary holding and manipulation of information. Park and Holzman (1992)initially reported that schizophrenia patients were impaired on several delayed response tasks (DRT), the classical working memory paradigm adapted from the animal literature (Hunter, 1913; Goldman-Rakic, 1987). Since then, several replications of spatial working memory impairment in schizophrenia have followed (Park and Holzman, 1993; Spitzer, 1993; Keefe et al., 1995; Carter et al., 1996; McDowell and Clementz, 1996; Fleming et al., 1997).

A considerable body of evidence implicates the involvement of dorsolateral prefrontal cortex (DLPFC) in delayed response tasks. Goldman-Rakic, 1987, Goldman-Rakic, 1991has written detailed reviews of the non-human primate literature, establishing the DRT as the paradigmatic task for the activation of delay-specific, directionally sensitive neurons in the principal sulcus region of the DLPFC. Further evidence for DLPFC involvement in delayed response tasks comes from animal lesion studies (Brozoski et al., 1979) and functional imaging techniques in humans (McCarthy et al., 1994; Sweeney et al., 1996; Courtney et al., 1998). Because of the solid empirical support for the spatial DRT as a measure related to prefrontal functioning, DRT impairment in schizophrenia adds strong converging evidence to the long-standing theory of frontal lobe dysfunction.

The question of how spatial working memory relates to performance on other traditional frontal lobe tasks in schizophrenia, however, has received little attention. In schizophrenia research, impairment on one or more executive or frontal tasks is often reported, but patterns of relationships between these measures remain elusive (Goldberg et al., 1988, Goldman-Rakic, 1991, Goldman-Rakic, 1994). Goldman-Rakic (1987), Goldman-Rakic (1991, 1994)and others (Kimberg and Farah, 1993; Pennington, 1994) have argued from a theoretical stance that working memory may be the cornerstone of executive functions, the underlying cognitive process that accounts for seemingly disparate patterns of impairments observed in schizophrenia patients and in individuals with frontal lobe damage. If working memory remains the common denominator of tasks sensitive to frontal dysfunction, one should observe substantial correlations between these measures and spatial DRT performance. Observing covariance would strengthen the case for a single, underlying deficit in schizophrenia patients (or perhaps a sub-group) that is linked to the integrity of the DLPFC. A lack of task associations would suggest that the commonly used `frontal' tasks are tapping disparate cognitive processes and/or neuroanatomical systems in schizophrenia patients.

A few studies have examined relationships between working memory and other putative frontal tasks in schizophrenia patients. Park and Holzman (1993)reported a correlation of 0.51 between working memory performance on an oculomotor DRT and smooth pursuit eye movements (SPEM) in schizophrenia patients. Although the nature of the pursuit tracking impairment and the neuroanatomical substrates that subserve smooth pursuit remain unresolved, there is evidence of involvement of frontal cortical processes (e.g. frontal eye fields) in normal subjects engaged in smooth pursuit (Gersden et al., 1996; Petit et al., 1997) and in SPEM dysfunction in schizophrenia (Katsanis and Iacono, 1991; Grawe and Levander, 1995). Gold et al. (1997)found a strong correlation (r=0.74) between a verbal working memory task and the WCST category achieved score in schizophrenia patients after controlling for Full-scale IQ, but not with the WCST perseveration score. Seidman et al. (1995)reported significant correlations between WCST perseverative responses and patients' performance on an associative working memory task (delayed alternation).

No study has yet reported an association between WCST performance and a spatial delayed response task, which would provide further converging evidence that working memory is a key cognitive component of successful WCST performance. Furthermore, to our knowledge, no study has reported on the relationship between working memory and performance on another aspect of oculomotor functioning for which there is evidence of prefrontal involvement—the antisaccade task. This task requires subjects to inhibit a prepotent saccade to a suddenly appearing target in the periphery and direct their gaze to the opposite hemifield from the target. Schizophrenia patients have demonstrated antisaccade deficits (Clementz et al., 1994; Tien et al., 1996; Katsanis et al., 1997), as have neurological patients with prefrontal lesions (Guitton et al., 1985; Pierrot-Deseilligny et al., 1991). Functional imaging reports suggest prefrontal involvement in normal subjects (although precisely which prefrontal areas are involved is unclear; O'Driscoll et al., 1995; Sweeney et al., 1996). Therefore, the antisaccade task would be of interest to include in an investigation of the correlates of working memory in schizophrenia.

The aims of the present study were: (1) to replicate the finding that schizophrenia patients are impaired on the working memory components of a spatial delayed response task; and (2) to further characterize the relationships between working memory performance and other clinical and oculomotor tasks purportedly sensitive to frontal lobe functioning. We hypothesized significant correlations between working memory and performance on putative frontal neuropsychological tasks, including the WCST, a verbal fluency task and two measures of figural fluency. Other neuropsychological tasks purportedly sensitive to more posterior regions were used to test the specificity of the frontal deficit hypothesis. In addition, we predicted that working memory would correlate with two oculomotor measures of interest: smooth pursuit eye tracking and antisaccade task performance.

Section snippets

Participants

Forty-two schizophrenia inpatients were recruited from acute-care psychiatric units of a regional hospital that serves a large metropolitan area. All patients met DSM-IV (American Psychiatric Association, 1994) criteria for schizophrenia, based on diagnostic interviewing using the Structured Clinical Interview for DSM-IV (SCID, Modules A–E) (First et al., 1995) and chart reviews. SCID interviewers were advanced graduate students in clinical psychology, with specific training in interviewing and

Results

Table 1 summarizes the demographic and clinical characteristics of the subject samples. There were no significant differences between groups in age. Normal controls had a significantly higher mean education level than the schizophrenia patients [t(95)=6.38; p<0.0001]. The estimated FSIQ also differed significantly between the groups [t(90)=5.91; p<0.0001]. The lower IQ of the schizophrenia patients is consistent with documented reports in the literature indicating that their mean FSIQ is

Discussion

Consistent with other reports, this investigation demonstrated impairment in schizophrenia patients on the working memory component of a spatial delayed response task. This study contributes further to the spatial working memory literature by including a sensory–motor control condition, multiple delay periods, as well as an 8-s delay with and without an intervening distraction task. Although the schizophrenia patients tended to demonstrate a worse performance than controls during the 0.5-s and

Acknowledgements

This research was supported by grants from the National Institute of Mental Health (MH 49738 and MH 17069) and the National Alliance for Research on Schizophrenia and Depression.

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    1

    Present address: Minneapolis Veterans Affairs Medical Center, Cognitive Neuroimaging Unit (IIP), One Veterans Drive, Minneapolis, MN 55417, USA.

    2

    Present address: Department of Psychiatry, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA.

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