CommentaryComparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage
Introduction
Neuropsychological studies of patients with schizophrenia have consistently identified deficits on tests of executive function, traditionally considered sensitive to frontal lobe damage (Kolb and Whishaw, 1983; Stuss et al., 1983) (Taylor and Abrams, 1984, Taylor and Abrams, 1987; Weinberger et al., 1986, Weinberger et al., 1988; Pantelis et al., 1997). Deficits of executive function are characterised by impairments in planning, maintenance of goal-directed behaviour and behavioural flexibility. Tasks employed to assess different aspects of executive function have often used attentional set-shifting paradigms, such as the Wisconsin Card Sorting Test (WCST) (Berg, 1948). In these paradigms, subjects are required to shift attention between different stimulus dimensions on the basis of reinforcing feedback. It is proposed that patients with frontal lesions are impaired in their ability to inhibit previously learned responses and, as a consequence, are unable to shift their attention to the relevant stimulus, thus making errors of perseveration (Milner, 1963).
It has been demonstrated that patients with schizophrenia also perform poorly on tasks of attentional set-shifting (Kolb and Whishaw, 1983; Weinberger et al., 1986; Goldberg et al., 1987; Morice, 1990). In general, the results indicate that patients with schizophrenia achieve fewer sorting categories than controls and display significantly more perseverative errors. The common explanation provided for this performance is that patients with schizophrenia make perseverative errors due to a failure to inhibit inappropriate responses (Pantelis and Brewer, 1996). On the basis of these findings, parallels have been drawn between patients with schizophrenia and those with frontal lobe damage and it has been inferred that set-shifting deficits in patients with schizophrenia are indicative of frontal lobe dysfunction. However, it remains unclear whether patients with schizophrenia fail these tasks because of the same underlying cognitive deficit as frontal lobe patients. One strategy to help elucidate the nature of the deficits in schizophrenia is directly to compare performance with that of other neurological patients (Randolph et al., 1993), as in some recent studies (Gold et al., 1994; Heaton et al., 1994; Hanes et al., 1996a, Hanes et al., 1996b; Pantelis et al., 1997). However, no recent study has directly compared patients with schizophrenia and frontal lesion patients on tests of set-shifting ability.
A second issue arising from studies of set-shifting which use the WCST, is that successful performance requires motivational, attentional, memory, and learning processes, in addition to or instead of intact executive function (Downes et al., 1989). Therefore, similarly poor performances between patients with schizophrenia and patients with specific brain lesions may reflect very different underlying cognitive deficits, as suggested in a positron electron tomography (PET) study comparing patients with schizophrenia and Huntington's disease matched for WCST performance (Goldberg et al., 1990). Recent studies have attempted to separate this complex task into its component cognitive processes. Two types of set-shift have been proposed (Downes et al., 1989): intra-dimensional shifts (IDS), which involve the transfer of a rule within the same stimulus dimension (e.g. choosing circles instead of squares), and extra-dimensional shifts (EDS), which require a transfer of attention across different stimulus dimensions (e.g. choosing on the basis of colour rather than the previous category of shape). In essence, EDS shifting is the core component of the WCST, and is the basis for the achievement of novel sorting categories. IDS shifting is a more basic element of the WCST and is related to the ability of the subject to be aware of the conceptual category within which they are responding. A successful IDS shift requires a generalisation of learning or the ability to `learn set'. In an attempt to dissect these component processes involved in set-shifting, several recent studies have used a computerised version of the WCST that is graded in complexity, and allows these processes to be separated (Roberts et al., 1987; Downes et al., 1989; Owen et al., 1991).
The present study set out directly to examine set-shifting ability in schizophrenia and to compare this with patients with frontal lobe lesions. Previous studies using the computerised set-shifting task have shown that patients with frontal lobe damage are impaired at the EDS shifting stage (Owen et al., 1991) and that their responses are perseverative (Owen et al., 1993). Two studies have used a related paradigm to assess patients with schizophrenia (Elliott et al., 1995; Hutton et al., 1998). While Hutton et al. (1998)found that first-episode patients were relatively unimpaired in set-shifting ability, Elliott et al. (1995)demonstrated that patients with established schizophrenia were perseverative, with apparent similarities to the performance observed in patients with frontal lobe lesions. However, as age, education, and IQ vary considerably between psychiatric and neurological patient groups, correct inferences require direct matched comparisons, as in the present study.
The current investigation further set out to address methodological issues in the analysis of set-shifting behaviour. Previous studies using the computerised paradigm have typically analysed the data for attrition rate in a cumulative manner; that is, examining the overall number of patients who had failed the task by a particular stage, as opposed to the actual number who failed at that level. This type of analysis assumes that a patient failing a specific stage will also fail each subsequent stage. Additionally in previous studies, when a subject failed a specific stage they were given the maximum error rate for each subsequent stage, even though they did not attempt them. Also, previous studies have not examined the performance of subjects actually passing any particular stage, in order to assess the level of difficulty encountered by different groups in attaining criterion. These assumptions and data analysis techniques may obscure subtle performance differences between patients who fail at different stages of the test. Importantly, many studies have shown that patients with schizophrenia are not homogeneous in their cognitive deficits (e.g. Seidman, 1990; Shallice et al., 1991; Braff et al., 1991; Anderson et al., 1991). Therefore, it is likely that different patients will fail at different stages and this will reflect different cognitive abnormalities. Previous work has suggested that such variation may reflect the heterogeneous symptomatology which characterises the disorder, and that different patterns of neuropsychological impairment are associated with particular symptom or behavioural profiles (Liddle, 1987a; Liddle and Morris, 1991; Brewer et al., 1996; Pantelis and Brewer, 1995, Pantelis and Brewer, 1996; Norman et al., 1997). Therefore, in the present investigation we also investigate the qualitative aspects of performance specifically for those patients who passed at each stage. In this way we were able to examine, first, whether there were subgroups of patients with schizophrenia who could be identified on the basis of their performance on set-shifting; and second, whether these subgroups also differed in terms of their symptomatological and behavioural profile.
Section snippets
Patients with schizophrenia
A detailed description of the selection of patients with schizophrenia has been provided elsewhere (Pantelis et al., 1997). Patients were excluded if there was recent drug abuse as assessed with urine drug screening, poor eyesight, history of significant head injury, epilepsy, leucotomy, or other neurological disorder, or significant medical condition considered to affect cognitive performance (including thyroid disease) (detailed in Pantelis et al., 1997). Fifty-one patients (43 males, 8
Attrition rates: cumulative (Fig. 2a)
Significant group differences emerged at the IDS and IDR stages (IDS: 2i=14.32, df=2, p<0.001; IDR: 2i=21.07, df=2, p<0.00005) and the EDS and EDR stages (2i=23.15, df=2, p=0.00001). Further investigation revealed that the effect was due to an increased number of failures in the patients with schizophrenia, as compared with the other two groups at the IDS and EDS stages (schizophrenia vs controls: IDS: 2i=13.50, df=1, p<0.0005; IDR: 2i=18.87, df=1, p<0.0005; EDS and EDR: 2i=23.13, df=1, p
Discussion
The results of this study, comparing patients with schizophrenia with both frontal lesion patients and matched control subjects, show striking differences in the profiles of the two patient groups on the set-shifting paradigm. While significantly more subjects in both patient groups failed at the extra-dimensional (EDS) stage of the task compared with controls, by far the majority of patients with chronic schizophrenia were unable to reach criterion by the earlier intra-dimensional shift (IDS)
Acknowledgements
We would like to thank C.E. Polkey and P.N. Leigh who referred patients with frontal lobe lesions, detailed data for which have been published, as cited in the text. We thank Jo Iddon for her invaluable help with a number of data queries. We thank Dr Paul Maruff and Rosemary Purcell for their comments. We also thank Susan Tanner, Lisa Weatherley, Susan Bodger and Sı̂an Thrasher for their help with the study. Financial support for this study was provided by the Horton Hospital League of Friends
References (77)
- et al.
Cognitive functioning and positive and negative symptoms in schizophrenia
Schizophr. Res.
(1991) - et al.
Differential relationships between positive and negative symptoms and neuropsychological deficits in schizophrenia
Schizophr. Res.
(1997) - et al.
Neuropsychological, olfactory and hygiene deficits in men with negative symptom schizophrenia
Biol. Psychiatry
(1996) - et al.
Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson's disease: evidence for a specific attentional dysfunction
Neuropsychologia
(1989) - et al.
Mini mental state: a practical method for grading the cognitive state of patients for the clinician
J. Psychiatr. Res.
(1975) - et al.
Subcortical dysfunction in schizophrenia: a comparison with Parkinson's disease and Huntington's disease
Schizophr. Res.
(1996) - et al.
Planning and spatial working memory following frontal lobe lesions in man
Neuropsychologia
(1990) - et al.
Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man
Neuropsychologia
(1991) - et al.
Neuropsychological and olfactory dysfunction in schizophrenia—relationship of frontal syndromes to syndromes of schizophrenia
Schizophr. Res.
(1995) - et al.
Cerebral perfusion correlates of negative symptomatology and parkinsonism in a sample of treatment-refractory schizophrenics: an exploratory 99mTc-HMPAO SPET study
Schizophr. Res.
(1997)
Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type
Neuropsychologia
Wisconsin Card Sorting Test performance as a measure of frontal damage
J. Clin. Exp. Neuropsychol.
A simple objective treatment for measuring flexibility in thinking
J. Gen. Psychol.
The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results
Arch. Gen. Psychiatry
Syndromes of chronic schizophrenia and some clinical correlates
Br. J. Psychiatry
Specific cognitive flexibility rehabilitation in schizophrenia
Psychol. Med.
Dissociation in prefrontal cortex of affective and attentional shifts
Nature
Primate analogue of the Wisconsin Card Sorting Test—effects of excitotoxic lesions of the prefrontal cortex in the marmoset
Behav. Neurosci.
The neuropsychology of schizophrenia: relations with clinical and neurobiological dimensions
Psychol. Med.
Neuropsychological evidence for frontostriatal dysfunction in schizophrenia
Psychol. Med.
Specific neuropsychological deficits in schizophrenic patients with preserved intellectual function
Cognitive Neuropsychiatry
The performance of young schizophrenics and young normals on the Wisconsin Card Sorting Test
J. Consult. Psychol.
Schizophrenia and temporal lobe epilepsy. A neuropsychological analysis
Arch. Gen. Psychiatry
Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test
Arch. Gen. Psychiatry
Regional cerebral blood flow and cognitive function in Huntington's disease and schizophrenia. A comparison of patients matched for performance on a prefrontal-type task
Arch. Neurol.
Teaching the Wisconsin Card Sorting Test to schizophrenic patients
Arch. Gen. Psychiatry
Wisconsin Card Sorting Test performance in schizophrenia: remediation of a stubborn deficit
Am. J. Psychiatry
Bradyphrenia in Parkinson's disease, Huntington's disease and schizophrenia
Cognitive Neuropsychiatry
Neuropsychological deficits in schizophrenics. Relationship to age, chronicity and dementia
Arch. Gen. Psychiatry
Executive function in first episode schizophrenia
Psychol. Med.
Schizophrenia patients discharged from hospital—a follow up study
Br. J. Psychiatry
Executive function in first episode schizophrenia: improvement at one year (Abstract)
Schizophr. Res.
Performance of schizophrenic patients on tests sensitive to left or right frontal temporal, or parietal function in neurological patients
J. Nerv. Ment. Dis.
Cited by (323)
Executive dysfunction and cognitive decline, a non-motor symptom of Parkinson's disease captured in animal models
2024, International Review of NeurobiologyCortico-cognition coupling in treatment resistant schizophrenia
2022, NeuroImage: ClinicalLongitudinal subtypes of disordered gambling in young adults identified using mixed modeling
2020, Progress in Neuro-Psychopharmacology and Biological PsychiatryThe psycho-periodic cube
2019, Medical Hypotheses