Smadar Levin, Deborah Yurgelun-Todd, Suzanne Craft. Journal of Abnormal Psychology. Volume 98, Issue 4, November 1989.
Clinical neuropsychological findings are examined with respect to competing hypotheses about localized neuropathology in schizophrenia. Two general models of structural and functional impairment are described. The first addresses deficits in cortical/subcortical processes concerned with arousal, attention, and higher cortical functions. The second addresses impairments in the balance of lateralized functions consistent with left hemisphere overactivation. Empirical data provide support for both models, and suggest that the explanatory power of these models may vary when they are applied to different subtypes of schizophrenia.
Recent advances in the neurosciences, especially in the study of neural connections, neurotransmitter pathways, and cell physiology (Bousefield, 1985; Iversen, 1985), have stimulated a growing interest in the neuropathology of psychiatric illnesses. Studies of brain dysfunction in schizophrenia have yielded evidence for neuropsychological and psychophysiological dysfunctions, as well as for biochemical and structural abnormalities (Holzman, 1985; Snyder, 1982; Stevens, 1982; Weinberger, Wagner, & Wyatt, 1983). These findings have led to propositions that schizophrenia is associated with a subcortical dysfunction (Mirsky, 1969; Patterson, 1987), a lateralized dysfunction (Gruzelier & Flor-Henry, 1979; Gruzelier, Seymour, Wilson, Galley, & Hirsch, 1988), a left hemisphere deficit (Gur, 1977), left hemisphere overactivation (Gur, 1978; Walker & McGuire, 1982), impaired interhemispheric integration (Bigelow, Nasrallah, & Rauscher, 1983; Craft, Willerman, & Bigler, 1987) and frontal dysfunction (Levin, 1984a, 1984b; Seidman, 1983). To test these propositions, many investigators have recently turned to neuropsychological paradigms. The purpose of this article is to describe and evaluate these efforts.
The potential contribution of neuropsychology to elucidating hypotheses of localized neuropathology in schizophrenia is considerable. In patients with known brain damage, neuropsychology has been aided in localization of brain dysfunction by other methods of diagnosis, such as the computerized tomography (CT) scan. Thus, a large body of research comparing neurobehavioral and neuropsychological patterns among patients with similar lesions has accrued. Although variability in anatomic structure, sex, handedness, age, etiology of lesion, and measurement techniques limit their conclusions, neuropsychological studies of brain damaged populations have yielded useful brain–behavior correlates (Kertesz, 1983) that might be fruitfully applied to the study of schizophrenia.
An additional contribution of the clinical neuropsychological approach is in describing the functional deficits and strengths of subject groups. This strategy is made possible by qualitative analyses of error patterns and performance styles, rather than the exclusive reliance on test scores and levels of overall performance (Milberg, Hebben, & Kaplan, 1986; Weiss & Seidman, 1988).
Neuroanatomical studies of schizophrenia have not yet identified a specific brain lesion related to the disorder. Although some investigators have indicated structural changes in the schizophrenic’s brain, there is no conclusive evidence for the presence of a consistent lesion. Thus, it appears that technological or methodological advances may be required before such studies yield precise and specific localization. At present, however, one can and should expect a neuropsychological paradigm, particularly one that provides data on performance styles and patterns, to describe consistent functional syndromes. Relying on brain–behavior correlates from the neurological literature, we can cautiously propose and evaluate hypotheses identifying dysfunctional brain systems in schizophrenia. We wish to underscore the term brain systems and to emphasize that attempts to localize dysfunction to specific brain structures, rather than to interrelated systems of brain structures, may be severely limited by methodological and conceptual problems to be discussed. This article reviews findings that shed light on hypothesized structure/function systems that may be abnormal in schizophrenia. Although the review focuses primarily on recent studies that used clinical neuropsychological measures with the goal of identifying structure/function correlations, findings derived from cognitive, experimental, or psychophysiological research will be considered if they directly contribute to the localization of impaired structure/function brain systems and if they are interpretable in the context of clinical measures.
The recent interest in neuropsychological research in psychopathology has arisen against a background of this approach’s rather disappointing history. The empirical battery approach, characteristic of early investigations of neuropsychological dysfunction in schizophrenia, investigated whether patients with “functional” disorders could be distinguished from patients with “organic” disorders on the basis of summary scores derived from standard test protocols such as the Halstead Reitan Battery (HRB) or the Luria-Nebraska Neuropsychological Battery (LNNB; Chelune, Heaton, Lehman, & Robinson, 1979; Golden, 1977; Goldstein & Halperin, 1977; Heaton, Baade, & Johnson, 1978; Malec, 1978; Wysocki & Sweet, 1980). It is clear that such studies may be limited by methodological and theoretical considerations. For example, neurologic patients of varying etiologies are often combined into one organic group. In addition, the assumption that schizophrenics should differ from certain neurological patients may be incorrect, given the hypothesis of underlying brain pathophysiology in this disorder. Despite these limitations, several general conclusions can be drawn from these studies. First, schizophrenics can usually be differentiated from neurological patients with documented brain damage, in that the latter have significantly lower global performance scores (Moses, Cardellino, & Thompson, 1983; Moses, Thompson, Cardellino, & Johnson, 1983). Few of the studies included normal control groups or nonschizophrenic psychiatric control groups; thus, it is unclear whether schizophrenics are more impaired than either of these control groups.
A second conclusion is that impaired performance on these tests is more characteristic of chronic than of acute schizophrenics (Golden et al., 1983). This conclusion, which is consistent with Heaton et al.’s (1978) review of earlier studies, suggests that it is important to examine neuropsychological dysfunction in subgroups of patients, and particularly in chronic schizophrenics. This observation is important, in that it emphasized the likelihood of brain dysfunction in schizophrenia and marked a shift from earlier views that psychosis was a functional disturbance. Despite these conclusions, however, very little additional knowledge has been gained through the use of the empirical battery approach in the past decade, and further investigation cast in this mold is likely to be similarly uninformative.
A more useful approach involves testing specific neuropsychological functions in schizophrenia. This method yields information about the type as well as the level of neuropsychological impairment. In the function-oriented approach, investigators typically measure specific neuropsychological processes such as verbal recall or visuoconstructional ability. A basic premise of this approach is that the behaviors measured by these tests are associated with specific brain regions (Kolb & Whishaw, 1983).
Several reviews have searched for patterns emerging from function-oriented neuropsychology studies. Seidman’s (1983) review of neuropsychological, neuroradiological, and neurophysiological studies proposed that brain dysfunction in schizophrenia was related to changes in the activation of a cortico-subcortical, arousal-attention system that includes brain-stem limbic and frontal-temporal areas. He also noted the consistency of this proposal with Ingvar’s (1976) hypothesis that the primary deficit may involve the mediothalamic frontocortical network, which activates anterior systems and inhibits transmission of afferent impulses to posterior areas. Furthermore, he suggested that two diagnostic/clinical subtypes were associated with specific patterns of neuropathology: nuclear or chronic schizophrenics, who have negative symptoms and reduced cortico-subcortical activation, and reactive or episodic schizophrenics, who have positive symptoms and increased activation of the cortico-subcortical system.
Mirsky and colleagues have also proposed and refined a theory of neuropathology in schizophrenia that focuses on a dysfunctional network subserving attentional processes (Mirsky, 1969, 1988). This network includes prefrontal, inferior parietal, and superior temporal cortex; limbic areas, such as the hippocampus and anterior cingulate; subcortical areas, such as the basal ganglia and midline reticular nucleus of the thalamus; and brain-stem areas, such as the tectum and mesopontine reticular formation. Mirsky emphasizes the interrelatedness of this system and suggests that its wide distribution makes it more susceptible to disruption. The manner in which such a disruption may be manifest will be discussed under the section on attention.
In a review of experimental neurobehavioral studies in schizophrenia, Levin (1984a) proposed a dysfunction of frontal lobe mechanisms that mediate attention and motor behavior, specifically those involving the mesocortical dopamine projections to the dorsolateral frontal cortex, as well as the subcortical inputs to the same region, such as the thalamic mediodorsal nucleus. Reviewing cognitive and neuropsychological data, she further proposed a hypothetical attention system and suggested that dysfunctions reported across studies may have been caused by impairments of various components of this system (Levin, 1984b). She noted that distractibility, inability to focus attention, slowness in nonreflexive responses, and perseveration were commonly the basis for poor performance patterns demonstrated by schizophrenics, and that these impairments were frequently associated with poor arousal and decreased motivation. Pointing to the phenomenological similarity between attention deficits in schizophrenia and in patients with frontal lobe lesions, Levin proposed that some schizophrenics suffer from a dysfunction of frontal feedback mechanisms mediating introceptive and extroceptive responses.
Both Seidman (1983) and Levin (1984b) noted that negative symptoms, such as social withdrawal, blunted affect, distractibility, apathy, and loss in initiative, may be associated with frontal impairment, because patients with frontal lobe lesions demonstrate many of these behaviors. This hypothesized association between attention and the frontal lobes will be discussed further in later sections of this article.
Another model of neuropsychological impairment in schizophrenia also suggests a frontal system as the locus for the dysfunction. Weinberger and colleagues noted that the dorsolateral prefrontal cortex has been shown to be functionally altered in schizophrenics (Weinberger, Berman, & Zec, 1986) and proposed that a dysfunction of the dorsolateral prefrontal system could account for both cognitive deficits and behavioral responses observed in these patients. Specifically, they hypothesized that a subtle lesion in dorsolateral prefrontal cortex (DLPFC) or in its periventricular limbic–diencephalic connections may cause a disruption of the dopaminergic innervation of this system, resulting in dopamine hypoactivity of the prefrontal cortex and concomitant hyperactivity of limbic structures.
A different model was proposed by Walker and McGuire (1982) in their review of intra- and interhemispheric processing in schizophrenia. In agreement with previous reviewers, they concluded that the data were consistent with left hemisphere overactivation (Gruzelier & Flor-Henry, 1979; Gur, 1977; Taylor, Greenspan, & Abrams, 1979), and did not support an alternative model of impaired interhemispheric integration. This latter model, which developed as a result of observations that the corpus callosum was measurably thicker in chronic schizophrenics (Bigelow, Nasrallah & Rauscher, 1983; Rosenthal & Bigelow, 1972), relies heavily on electrophysiological and neuroanatomical data. In addition, those few studies using clinical neuropsychological measures have frequently found patterns of lateralized deficits that interact with interhemispheric impairment (Craft et al., 1987). For these reasons, the interhemispheric integration model will not be considered separately in this article.
A recent theory of lateralized dysfunction in psychosis, referred to as the hemisphere imbalance syndrome model has been developed by Gruzelier and colleagues (Gruzelier, 1984; Gruzelier et al., 1988). According to this model, syndromes characterized as predominantly active reflect greater functional integrity of left fronto- and temporo-hippocampal systems, whereas withdrawn or negative syndromes reflect corresponding right hemisphere superiority.
Two general models of structural and functional impairment in schizophrenia are thus evident from these reviews. One model proposes deficits in the cortical/subcortical processes that support attention, arousal, and higher cortical functions. The second suggests an impairment in the balance of lateralized functions, which is consonant with left hemisphere overactivation. These models can be viewed in terms of a brain systems approach. Each model is based on an extended network of regions that together subserve identifiable neuropsychological processes. Functional deficits of the systems proposed, therefore, reflect pathology within the neural system but not a discrete localized lesion, because any disturbance along a stream of neural connections may result in grossly similar behavioral pathology. Using function for an organizational scheme, we review here neuropsychological studies that have either explicitly or implicitly tested the models proposed above.
Attention
Attention deficits dominate clinical descriptions of the schizophrenic syndrome (Bleuler, 1950; Kraeplin, 1919). An impairment of attention is widely accepted both as a clinical symptom and as an underlying mechanism of other cognitive dysfunctions in schizophrenia. What has not been determined is whether it is a primary deficit associated with the illness or merely an epiphenomenon (Goldberg, 1985). Previous reviewers pointed out that attention is complex and cautioned investigators to specify conceptually and operationally what aspect of attention is under study (Neale & Cromwell, 1970; Neuchterlein, 1977; Zubin, 1975).
A number of propositions have been offered regarding the specific nature of attention impairments in schizophrenia (Gjerde, 1983; Neuchterlein & Dawson, 1984). One theory suggests that schizophrenics are unable to attend selectively to incoming stimuli. This impairment may be manifested by the inclusion of a greater number of relevant elements, by the inclusion of irrelevant elements, or by the inclusion of distorted information because the attended elements are less integrated into whole components.
Second, attentional deficits may be related to a generalized slowing of neurocognitive functions in schizophrenia. Slowed processing will limit the amount of relevant information that is taken in by the individual for any specified time frame. It has also been proposed that selective attention and vigilance are affected by the complexity of stimuli and the difficulty of stimulus discrimination. Both task difficulty and a slowed rate of cognitive processing will thus contribute to schizophrenics’ deficits in the encoding of information (Yates, 1966).
There are many theoretical perspectives on the role of attention in schizophrenia, but only a few studies have used clinical neuropsychological methods. One study used a digit span test to examine the relationship between intake of information to modulation of focused attention among paranoid and nonparanoid schizophrenics (Rund, 1982/1983). The experimental paradigm included a distractor and a nondistractor condition, because performance loss as a result of distraction indicates a loss of focused attention. Paranoid schizophrenics improved on the distractor test, relative to the nondistractor condition, and were in fact significantly better than normal. Nonparanoid schizophrenics, on the other hand, performed significantly worse than the paranoid patients and normal subjects on the distractor test. Thus, a deficit in modulating focused attention is characteristic of nonparanoid patients and not of schizophrenic illness in general. These findings are consistent with previous reports that some schizophrenics perform poorly on measures with distractor conditions (Oltmanns, 1978; Pogue-Geile & Oltmanns, 1980) and support Seidman’s (1983) proposal that one subgroup of schizophrenics may suffer from an underarousal of a subcortical activation system, and a second subgroup may suffer from increased activation of this system. Furthermore, this study underscores the importance of examining clinical subgroups in investigations of neuropsychological dysfunctions.
Several recent studies looked at the association of attentional performance to positive and negative symptoms. Green and Walker (1986) used a digit span task and a dichotic listening task with and without distractors to examine the relationship between selective attention and positive and negative symptoms in schizophrenia. Patients’ ability to attend selectively was measured by several variables, including the number of intrusion errors produced. There was no evidence for lateralized dysfunction, given that the groups did not differ in dichotic listening performance. On the digit span task, however, there were differential impairments. Positive-symptom schizophrenics had the highest number of intrusions in the distractor condition, compared with other groups and compared with themselves in the nondistractor condition. Bipolar patients also had a significant increase in intrusions in the distractor condition. No significant differences were noted across conditions for normal subjects or other patients. Arguing that intrusion errors are measures of susceptibility to distraction the authors concluded that both positive-symptom schizophrenics and bipolar patients, but not negative-symptom schizophrenics, are vulnerable to distraction and display impaired selective attention.
These studies suggest that measures of attentional systems discriminate between schizophrenics with positive and negative symptoms. These findings support Seidman’s (1983) and Levin’s (1984b) arguments that differential attentional deficits may be expected among negative-symptom patients, who may have a frontal-cortical dysfunction, as opposed to among positive-symptom schizophrenics, who may have a subcortical dysfunction (Seidman) or a parietal-cortical dysfunction (Levin, 1984a, 1984b).
Stuss, Benson, Kaplan, Weir, & Della Malva (1981) examined sustained mental activity and attention of leucotomized schizophrenics, nonleucotomized schizophrenics, and normal control subjects. The research protocol included three subtests from the Wechsler Memory Scale, Form I (Serial Sevens, Digit Span, forward and backward; Wechsler, 1945) Knox Cube Imitation Test (Arthur, 1947), Object Span (Wells & Ruesch, 1969), Trail-Making Test ( Army Individual Test Battery, 1944), and the Stroop Test (Stroop, 1935). The greatest impairment was seen in the nonleucotomized schizophrenic group. Among the leucotomized patients, only the “nonrecovered” group showed impaired attention.
The authors concluded that deficits in attention were related to the presence and severity of schizophrenic symptoms, and not to the presence of chronic bifrontal lesions. These results are intriguing but do not necessarily argue against the role of frontal pathology in schizophrenia, because the number of subjects per group is too small (4–5) to determine whether there was a selection bias among the recovered and nonrecovered leucotomy patients. Furthermore, as the authors themselves suggest, a leucotomy may negate the underlying schizophrenic process, so that frontal system dysfunction is in effect “normalized” by the surgical lesion.
The greatest body of research on attention in schizophrenia consists of studies of information processing. These studies include measures of vigilance, sustained attention, and readiness to respond, assessed by tests such as the Continuous Performance Test (CPT; Rosvold, Mirsky, Sarason, Bransome, & Beck, 1956) and reaction time. This literature is vast, and for the most part no attempt is made to delineate structure–function correlations. The results of such studies will not be reviewed here. Nevertheless, it is important to acknowledge the potential contributions of this work to the neuropsychology of schizophrenia. For example, attentional deficits have been identified as vulnerability markers in remitted schizophrenic patients and high-risk relatives and can be used in genetic studies of neuropsychological dysfunction (Asarnow & MacCrimmon, 1981; Cornblatt & Erlenmyer-Kimling, 1985). Moreover, information processing studies of attention in schizophrenia, when interpreted in line with contemporary models of normal cognition, have generated several new models of cognitive deficits in schizophrenia. For example, Neuchterlein and Dawson (1984) pointed out that new models of selective attention are no longer based on sequential stage processing but on the “flexible allocation” of finite processing resources. An attentional model that proposes limited processing resources and flexibility in distribution of resources suggests that impairment may be a consequence of either reduced flexibility in the allocation of attention, or processing demands that exceed available resources. This conceptual framework may be useful in the interpretation of neuropsychological data and the formulation of future experimental paradigms (George & Neufeld, 1985, 1987).
The work of Mirsky and his colleagues goes beyond the isolated information processing approach in its careful attempt to explicate the neural systems underlying vigilance and their involvement in schizophrenia. To identify core deficits that predate the onset of manifest schizophrenia, Mirsky conducted prospective studies of high-risk children (Mirsky, Silberman, Latz, & Nagler, 1985). Using attentional measures, Mirsky et al. found that probands who received a schizophrenic spectrum diagnosis at age 26 demonstrated greater impairment on a vigilance task at age 11. This deficit is believed to be the consequence of a disruption of the neural system underlying attentional processes, which, as described previously, includes both cortical and subcortical components (Mirsky, 1988).
One of the most promising trends in current research is an integrated approach, emerging from the convergence of cognitive psychology, experimental psychopathology, and clinical neuropsychology. An example of this approach is seen in a recent report by Posner and his colleagues on directed visual attention in schizophrenics (Posner, Early, Reiman, Pardo, & Dhawan, 1988). These authors investigated visual attention to a target appearing in left and right visual fields in valid-cue, invalid-cue, and no-cue conditions. They found that schizophrenics’ response times were slower than those of normal subjects on invalid cue trials when the target appeared in the right visual field. This response pattern implies that the schizophrenics have difficulty disengaging and redirecting attention to the right visual field when it is first drawn away. Schizophrenics also showed difficulty attending to a verbal stimulus when a conflicting nonverbal stimulus was present. Their performance on both of these tasks was similar to patterns observed in patients with left hemisphere lesions (Posner, Walker, Friedrich, & Rafal, 1984). The authors interpret their results as indicative of a deficit in the anterior system that coordinates language and visual attention, and they speculate that this system may include the ventral striatum and anterior cingulate.
In summary, attentional deficits have been identified in schizophrenic patients using a range of assessment techniques. Despite the multifactorial nature of attention tests and the variability in task demands across studies, several conclusions can be drawn. The first is that attentional deficits are consistent with the models proposing frontal system dysfunctions in schizophrenia (Levin, 1984a, 1984b; Seidman, 1983; Weinberger, 1987). Second, clinical subgroups of schizophrenics differ in attentional abilities. The performance of nonparanoid and negative-symptom patients is consistent with reduced arousal and distractibility that is characterized by errors of omission and a greater number of incorrect responses. Paranoid and positive-symptom schizophrenics, on the other hand, display a deficit that is characterized by errors of commission such that their performance is at times even better than that of normal subjects. These subtype differences are also consistent with the propositions of differential attention deficits in patients with negative and positive symptoms (Levin, 1984b; Seidman, 1983). Third, there is evidence of lateralized deficits in the disengagement and redirection of visual attention. Finally, models of normal cognitive functioning have led to the interpretation of neuropsychological deficits in schizophrenia in terms of flexible distribution of attention with limited processing capacity.
Although a substantial body of work relating attention dysfunction to schizophrenia has been heuristic, it provides a strong foundation against which neuropsychological findings in attentional dysfunction may be interpreted. The theoretical perspectives reviewed by Seidman (1983), Levin (1984a, 1984b), and Neuchterlein and Dawson (1984) have incorporated both neurobiology and cognitive theory and have led to a greater understanding of attentional deficits in the context of a complex neurocognitive network.
Executive
Executive functions are cognitive processes that allow the subject to respond and adapt appropriately to his or her environment (Walsh, 1985). These functions include the preparation and execution of action, the initiation and modulation of activity level, the integration of behaviors into purposeful activity, and the maintenance of level of arousal. From a neuropsychological point of view, executive functions have been described as the ability to get into the appropriate response set for a given task, to maintain that set, and to shift set as needed. Executive functions are believed to be mediated by the frontal lobes (Stuss & Benson, 1983). In using the term executive rather than frontal lobe functions, we acknowledge that although the functions are mediated by the frontal lobes, they may involve distal cortical and subcortical sites in the frontal lobe’s neural circuitry. Thus, an impairment in executive functions can occur without structural changes in the frontal lobes (Goldberg, 1985; Goldberg & Bilder, 1987).
Impairment in frontal function has been documented in several studies that used comprehensive neuropsychological batteries. Kolb and Whishaw (1983) assessed schizophrenic and normal control subjects with the use of a battery of neuropsychological tests that were previously validated with neurological patients. They found that, as compared with the performance of normal control subjects, schizophrenics’ performance was impaired on tests measuring right- and left-frontal and temporal functions. In contrast, schizophrenics displayed normal performance on parietal lobe measures. These results were interpreted as suggestive of bilateral frontal and temporal deficits in schizophrenic patients.
Similar findings were reported by Taylor and Abrams (1984). These investigators compared schizophrenic patients and normal control subjects with the use of a variety of neuropsychological tests, including the Luria-Nebraska Battery (Golden, Hammeke, & Purisch, 1980), an aphasia screening test, and visuoconstructional tests. They reported that the schizophrenic’s performance was consistent with dysfunction of the dominant fronto-temporal region, although deficits were seen bilaterally.
Despite the concurring results of these studies, the specificity of the findings to schizophrenia remains in question, given that both failed to include a psychotic control group. Thus, generalized effects of psychosis on neuropsychological performance cannot be ruled out. Furthermore, patients and control subjects were not matched on IQ or educational variables. Taylor and Abrams’ response to the first criticism was that in earlier studies (Abrams, Redfield, & Taylor, 1981; Taylor & Abrams, 1983; Taylor, Redfield, & Abrams, 1981) they found different patterns of cognitive impairment between affective and schizophrenic patients, which suggests that the findings of their more recent study (Taylor & Abrams, 1984) are specific to schizophrenia.
A recent study by Gruzelier et al. (1988) addressed the issue of deficit specificity by comparing schizophrenics and affective-disorder patients with normal subjects on a number of neuropsychological measures that had been previously found to be sensitive to lateralized lesions of the fronto-hippocampal and temporo-hippocampal systems in neurological populations. Neuropsychological performance was related to patterns of clinical symptomology to identify subtypes within the psychiatric groups. In general, schizophrenics showed relatively greater impairment of left temporo- and fronto-hippocampal systems. Different performance patterns were noted however, among subgroups of subjects. Schizophrenics who were characterized as actively exhibiting delusions, cognitive acceleration, and overactivity demonstrated relatively intact, and in some cases superior, performance on putative tests of left-frontal function such as word fluency, with accompanying deficits on tests of right hemisphere function. The reverse pattern was demonstrated by schizophrenics with a withdrawn syndrome, whose clinical presentation involved primarily negative symptomatology. Affective-disorder subjects showed greater impairment on spatial tasks, which the authors suggested was an indication of preferential involvement of right hemisphere systems. These results were interpreted as consistent with the hemisphere imbalance syndrome model (Gruzelier, 1984), which posits that active symptoms are manifestations of increased activation and functional integrity of the left hemisphere, whereas withdrawal symptoms indicate right hemisphere predominance.
Weinberger and his collaborators also documented impaired executive functions in schizophrenic patients and concluded that these deficits are associated with DLPFC dysfunction (Berman, Zec, & Weinberger, 1986; Weinberger, Berman, & Illowsky, 1988; Weinberger et al., 1986). In these studies, subjects performed the Wisconsin Card Sort Test (WCST; Grant & Berg, 1980) and a number-matching task while regional cerebral blood flow was being measured at five specific activation sites. Patients differed significantly from normal control subjects in the relative change of prefrontal activity during the WCST and number-matching tasks. Schizophrenics also displayed a significant inverse relationship between prefrontal blood flow and number of perseverative errors on the WCST. In addition, the results do not appear to be secondary to an attentional deficit, as no significant differences between schizophrenic and normal subjects were observed in relative DLPFC activation during a continuous performance task.
In a follow-up study designed to address the question of whether failure to activate prefrontal cortex was a nonspecific effect of patients’ inability to perform a difficult task, Berman, Illowsky, and Weinberger (1988) measured regional cerebral blood flow (rCBF) during performance of Raven’s Progressive Matrices (RPM; Raven, 1938) a complex test of nonverbal reasoning that is not believed to be mediated predominantly by the DLPFC. Normal subjects showed relative rCBF increases in posterior brain regions during the task. Schizophrenics showed the same basic pattern of activation, although increases from baseline did not reach statistical significance. These results contrasted with the WCST finding that schizophrenics’ rCBF activation actually decreased in DLPFC, whereas normal subjects increased significantly. On the basis of these studies, the authors concluded that a specific DLPFC dysfunction plays a major role in the pathophysiology of the schizophrenic syndrome.
The extent to which a dysfunction of the DLPFC contributes to reduced WCST performance or is associated with the presentation of schizophrenic illness has been the subject of controversy. Using the WCST, Drewe (1974) studied patients with documented frontal lobe lesions of diverse etiologies and suggested that the critical area underlying sorting behavior may be the medial frontal lobe area, as opposed to the dorsolateral or orbital areas.
Stuss and his colleagues (Stuss & Benson, 1983) attempting to examine the role of the orbitofrontal cortex in cognition, used a modification of the WCST test administration and found that three groups of schizophrenics with orbitofrontal leucotomies performed poorly on the second half of the test after the sorting strategy had been explained to them. In contrast, all groups, including normal control subjects, performed equally well on the first 64 cards of the test. The performance of a fourth group of leucotomized schizophrenics was too impaired to include in the analyses. Because of the association of schizophrenia and orbitofrontal lesions in one group, the absence of complete data in the schizophrenic group without lesions, and the non-representativeness of the sample, it is difficult to draw clear conclusions about the localization of WCST dysfunction from this study. It is notable, however, that the error pattern demonstrated by these patients differed from the perseverative responses typically associated with dorsolateral dysfunction (Milner, 1963, 1964). A qualitative analysis of performance indicated that in the second deck, despite clarification of the test strategy, orbitofrontal patients could not sustain consistent sequences of correct responses; that is, they were unable to maintain set. The authors suggested that orbitofrontal pathology underlies decreased performance that is due to loss of set on the WCST. In addition, they related leucotomized schizophrenics’ normal performance on the first half of the WCST test to a possible beneficial effect of the orbitofrontal lesion.
Goldberg, Weinberger, Berman, Pliskin, and Plodd (1987) also examined the effects of specific task instruction in an attempt to clarify attentional and motivational factors in schizophrenics’ WCST performance. Subjects were tested in block intervals with varying instruction between blocks depending on group assignment. The Selective Reminding Memory Task was used as a control task (Buschke & Fuld, 1974). The performance of the schizophrenic groups who received systematic instruction showed some improvement across test blocks but returned to baseline at retest, which suggests that the schizophrenics were unable to learn the task, although they did learn word lists in the Selective Reminding Task. The authors suggested that the fact that schizophrenics could use direct instruction but were unable to maintain learning indicates that poor performance on the WCST is consistent with prefrontal processing deficits and is not solely the consequence of poor motivation and attention. This study provided further evidence of an impairment of executive functions in schizophrenia, and argued against a nonspecific, generalized dysfunction.
To investigate the role of the psychotic process in WCST performance, Yurgelun-Todd, Craft, O’Brian, Kaplan, and Levin (1988) compared schizophrenics with psychotic bipolar patients and normal control subjects, using the modified Stuss procedure described above. During the standard administration of the first deck of 64 cards, schizophrenics produced significantly fewer correct responses and correct sorts (10 correct responses in a sequence). The bipolar patients displayed no significant impairment. On the second deck, schizophrenics again made fewer correct responses and sorts than did normal control subjects, thus replicating Goldberg et al.’s (1987) finding of impaired learning on this task. Bipolar patients, however, also performed significantly worse than did normal control subjects, although only on number of sorts completed and not on number of correct trials. The bipolar group did not differ significantly from the schizophrenics.
A qualitative evaluation of errors produced during the two-part task indicated that different processing strategies were used by the two psychiatric groups. In the first deck, both patient groups were unable to sustain a sequence and made perseverative errors, although neither group differed statistically from the normal control subjects on these qualitative measures. On the second deck, however, after the task was explained, schizophrenics had a significantly greater number of within-category perseverative errors, that is, a repeated error that is not consistent with a previously reinforced category. Bipolar patients, on the other hand, had a significant increase in failure to sustain the sequence, compared with normal control subjects. This pattern suggests that schizophrenics have poor mental flexibility, resulting in perseveration, whereas bipolar patients are unable to self-regulate and maintain a set. Thus, although an impairment of executive functions is not specific to schizophrenia, schizophrenic and bipolar patients have unique processing strategies, which suggests differential pathology in the frontal system.
Yurgelun-Todd and Levin (1988) also studied the performance of schizophrenics, psychotic bipolar patients, and normal control subjects on five measures with known sensitivity to frontal dysfunction (WCST [ Milner, 1963], Verbal Fluency [FAS; Spreen & Benton, 1969], Stroop Interference Test [ Stroop, 1935], Trailmaking A and B, and Reciprocal Motor Programs [ Christensen, 1979]). Performance on these tests was compared with performance on two nonfrontal measures (Benton Line Orientation [ Benton, Varney, & Hamsher, 1978] and Stroop Word Reading) and two measures estimating I.Q. (WAIS-R Vocabulary subtest, and WAIS-R Block Design subtest; Wechsler, 1981). Schizophrenics’ overall performance was significantly impaired on all tests; however, with the exception of performance on the Stroop Interference Test, there were no significant differences in mean test scores between schizophrenics and bipolar patients. An analysis of error patterns and processing style, however, revealed that schizophrenics’ errors demonstrated both a failure to inhibit and an increase in perseverative behavior, whereas bipolar patients’ errors primarily reflected failures in inhibition. Cluster analysis revealed that the poor performance of schizophrenics was restricted to a subgroup of patients, which suggests that there was heterogeneity within the schizophrenic sample. Another intriguing finding in this study was that schizophrenics showed significant correlations between IQ and frontal measures.
In summary, the studies reviewed here suggest that schizophrenics have significantly impaired executive functions. When a systems approach to executive functions is applied, these results are consistent with a dysfunction of a large network mediating arousal and attention. This system could be disrupted either by frontal cortical pathology associated with dorsolateral or orbitofrontal lesions, or by a dysfunction of subcortical–cortical system-mediating arousal. In addition, there is evidence suggesting that subtypes of schizophrenia may be associated with lateralization of executive functions.
The interpretation of these conclusions should be approached with caution. First, it is difficult to localize impaired executive functions, because pathology in other brain areas may result in “frontal impairment” (Goldberg & Bilder, 1987). Second, the relationship between impaired executive functions and generalized cognitive impairment as measured by IQ estimates remains to be clarified. Third, although it is unlikely that a generalized deficit accounts for schizophrenics’ poor performance on frontal measures, control measures and level of task difficulty have often varied between studies, which has precluded definitive tests of a generalized deficit hypothesis. Finally, the presence of executive dysfunction in bipolar patients suggests that prefrontal pathology is not specific to schizophrenia, although the data point to the impairment of different frontal mechanisms in the two psychotic conditions. Despite these cautions, the investigation of executive processing deficits has contributed significantly to our understanding of schizophrenic illness, and further gains will undoubtedly be made—for example, by defining cognitively similar subtypes, by correlating neuropsychological results with CT and magnetic resonance imaging findings, and by describing progressive changes in function paralleling treatment with medication.
Motor
Disturbances in voluntary and involuntary motor control, including incoordination, clumsiness, tremors, and posturing, are often observed in schizophrenic patients (King, 1969; Manschreck, 1986; Marsden, Tarsy, & Baldessarini, 1975), which suggests that such disturbances are a major component of the schizophrenic disorders (Rosenbaum, 1968).
Neuropsychological methods of motor assessment range from simple tasks, such as finger tapping and manual dexterity, to more complex perceptuo-motor tests, such as reaction time. One consistent finding in studies of psychomotility in schizophrenics is a slowing in response speed (Goldstein, 1986; King, 1969). Because many measures of motor function include both cognitive and motor components, the determination of pure motor slowing is not entirely straightforward. A common concern is that the assessment of motor function is confounded with attention, information-processing speed, and mental flexibility. For example, reaction time, a complex measure that involves both attention and motor speed, has been studied extensively in schizophrenia. We will not review this literature here, but we will mention briefly that reaction-time studies have shown that stimulus intensity and preparatory intervals affect schizophrenics’ motor speed differentially, which indicates that psychomotor behavior in schizophrenia is affected by attentional impairment.
King (1969) studied a “pure” measure of motor speed by asking subjects to lift their fingers off a reaction key. This lift-reaction time provided a measure of attention. Subjects then moved their hand to press a second key, and the traverse-reaction time was recorded as a measure of motor speed. King found that lift-reaction time, as well as specific measures of motor speed, such as traverse-reaction time, tapping speed, and finger dexterity, were all impaired in schizophrenic patients. This finding was not specific, however, because affective patients had similar deficits. Furthermore, for all the psychiatric subjects in King’s study, decreased psychomotor speed was associated with severity of illness.
Rosofsky, Levin, and Holzman (1982) replicated King’s findings, using multivariate analytic techniques. Severity of illness, however, was not found to be related to motor slowing. These studies suggest that motor dysfunction is not merely an epiphenomenon of attentional disturbance, though the two are associated. They also show that psychomotor slowing is not specific to schizophrenia but is associated with psychosis.
Merrin (1984) studied lateralized motor function by measuring bilateral grip strength in paranoid and nonparanoid schizophrenics, bipolar and unipolar affective disorder patients, and normal control subjects. He found that schizophrenics had lower than normal hand strength bilaterally but did not differ in this regard from affective patients. An index of lateralized motor strength based on the ratio of right- to left-hand strength indicated, however, that both paranoid schizophrenics and affective-disorder subjects showed a greater right-hand advantage than did normal subjects, whereas nonparanoid schizophrenics showed significantly less lateralization.
The finding of decreased bilateral motor strength is consistent with previous studies (King, 1969; Rosofsky et al., 1982) and supports a theory of bilateral frontal impairment in schizophrenia. The significant increase in relative right-hand grip strength observed in paranoid schizophrenics agrees with Gruzelier’s (1981) proposal that paranoid schizophrenics may display an overdependence on left hemisphere function, and is in accord with Walker and McGuire’s (1982) proposition that there is left hemisphere overactivation in some schizophrenics.
Handedness is also a measure of functional asymmetry. Studies of handedness in schizophrenia are too numerous to review here, and the reader is referred to previous reviews by Merrin (1981) and Shan-Ming et al. (1985). Handedness and motor-laterality studies have often produced conflicting results, which have been attributed to limited subject selection, unreliable diagnosis, and inconsistent methods of laterality assessment (Shan-Ming et al.).
In summary, the clinical observation of impaired motor behavior in schizophrenics is supported by empirical studies of psychomotor slowing. A recurrent concern in the assessment of motor behavior is the confound introduced by attentional variables. Using pure motor measures, several studies report significantly slowed bilateral motor response in schizophrenic subjects. Studies of motor laterality and handedness have yielded contradictory results, although there is some evidence for a left hemisphere overactivation in paranoid schizophrenics and affective-disorder patients. Moreover, psychomotor slowing is related to psychosis, although subtle differences in lateral motor strength are found between affective and schizophrenic patients.
The documentation of motor deficits that are independent of, but correlated with, cognitive/attention dysfunctions is consistent with Seidman’s (1983) and Levin’s (1984a, 1984b) models. A disturbance of the brain-stem arousal system could certainly lead to generalized motor slowing. This argument is weakened by evidence that slowing in schizophrenics may not be comparable across all forms of motor behavior. For example, Levin, Holzman, Rothenberg, and Lipton (1981) found that eye-movement reaction time is normal in schizophrenic patients who have abnormally slowed hand reaction times. Another possible explanation for observed motor deficits is that motor slowing is related to a dysfunction of frontal mechanisms of motor modulation, especially those subserved by thalamic and striatal connections with the prefrontal dorsolateral cortex (Levin, 1984a, 1984b). The extensive nature of the frontal motor/attentional system renders it vulnerable to disruption; therefore, it is not surprising that evidence for such a disruption may be observed in both the schizophrenic and affective disorders, and that, as a result, these two groups frequently perform similarly on gross neuropsychological measures. It is only as we refine our diagnostic categories and subtypes, as well as our measurement techniques, that subtle and consistent differences between the psychiatric groups appear.
The use of more sensitive techniques for assessment of sinistrality, combined with contemporary developmental models of laterality (Fein, Humes, Kaplan, Lucci, & Waterhouse, 1984; Soper & Satz, 1984; Soper et al., 1986) holds promise in the study of cerebral dysfunctions in schizophrenia.
Spatial Abilities
Findings of visuospatial impairment in schizophrenia have been inconsistent. Stuss, Benson, Kaplan, Della Malva, and Weir (1984) administered visuoperceptual and visuoconstructional tests to leucotomized and nonleucotomized schizophrenic subjects and normal control subjects. There were no differences between groups in copying simple designs. On tasks that required active integration of complex constructional elements, however, such as the Block Design or Object Assembly subtests of the Wechsler Adult Intelligence Scale (WAIS; Wechsler, 1955) nonleucotomized schizophrenics were significantly more impaired than either the leucotomized schizophrenics or normal subjects. The observation of intact simple perceptual and constructional abilities is consistent with the previously discussed results of Kolb and Whishaw’s (1983) findings of normal performance on tests of parietal function.
Visuospatial deficits on complex tasks have also been found by Yurgelun-Todd, Craft, Levin, Kaplan, and Aizley (1987) who compared schizophrenic, bipolar, and normal subjects’ copy of the Rey Osterrieth Complex Figure (Osterrieth, 1944). Measures of both accuracy and constructional style were derived from the copy condition as well as from immediate recall and 20-min-delayed recall conditions. In the recall conditions, both psychiatric groups showed a greater than normal degree of confabulation, defined as adding novel details to the drawing. The authors noted that, in the copy condition, this task requires primarily parietal-occipital mechanisms of visuoperceptual and constructional functions. In the recall conditions, however, when the drawing must be reconstructed from memory, right hemisphere-frontal mechanisms of organization and retrieval are involved in addition to temporal memory processes. Thus the finding is consistent with a dysfunction of right-frontal cortex. Cluster analytic technique revealed that the effect was specific to subgroups of patients in both schizophrenic and affective-disorder groups, which suggests heterogeneity with respect to visuoconstructional functions.
Heterogeneity is also suggested by evidence that spatial abilities are particularly impaired in schizophrenic patients without affective symptoms. Green and Walker’s (1985) findings suggest greater visuomotor deficits in schizophrenics with primarily negative symptoms. Craft, Yurgelun-Todd, Kaplan, Aizley, and Levin (1988) also found that deficits in visuoconstructional ability were more severe in schizophrenic patients without affective symptoms who also demonstrated impairment on frontal lobe tests. One interpretation of these findings is that frontal lobe impairment shown by negative-symptom schizophrenics may disrupt their ability to organize visuoconstructional tasks. In addition, impaired visuoconstructional ability is characteristic of patients with early and severe injury to either, or both, hemispheres (Lezak, 1983). It is believed that language functions are given predominance in terms of functional recovery following such injury, often at the expense of visuospatial processes.
Affect
A disturbance of affect in schizophrenic patients, including inappropriate or incongruent affect and the absence or flattening of affect, has frequently been noted. The hypothesis that flat affect and other negative symptoms may characterize an etiologically distinct subtype of schizophrenia (Andreasen, Olsen, Dennert, & Smith, 1982) has led to growing interest in the study of affect.
Neuropsychological studies indicate that a number of brain areas play a role in the determination of emotional states (Ross, 1981). To understand the relationship between affective experience and expressive behavior, it is important to determine whether inappropriate affect is the consequence of a deficit in emotional perception (decoding affective cues), impaired expressive ability (encoding), or both. Furthermore, it is important to distinguish between visuoperceptual deficits in general (e.g., facial features are not decoded) and emotional perception in particular (e.g., happy/sad/angry facial expressions are not decoded).
Addressing the latter question, Walker, McGuire, and Bettes (1984) administered tests of emotional and facial discrimination that required the ability to identify and verbally label emotion to schizophrenics, affective-disorder patients, and control subjects. They found significant differences between schizophrenics and normal control subjects on all measures of emotional discrimination and labeling, but not on facial discrimination. These findings suggest that schizophrenics’ impairment in decoding emotion is due to poor recognition of facial emotion and verbal labelling, but not to visuoperceptual deficits.
Feinberg, Rifkin, Schaffer, and Walker (1986) also examined facial discrimination, recognition of facial emotions, and verbal labelling of emotion. They included a control test for difficulty of visual discrimination, which consisted of photographs of inverted faces. Schizophrenics performed significantly worse than normal control subjects on all four tests. Schizophrenics also performed significantly worse than the depressed control group on the recognition of facial emotion. These results support Walker et al.’s (1984) finding that schizophrenics have deficits in both identifying and verbally labelling facial emotion. Feinberg et al.’s finding of poor discrimination of inverted faces in schizophrenics also points to a deficit in complex visual perception that may contribute to poor affect decoding. It is possible, however, that discrimination of inverted faces is more difficult than discrimination of comparably complex nonfacial stimuli. Moreover, inverted faces may not be pure visuospatial stimuli, but rather, may contain emotional information.
In addition to studies of visual decoding of affective stimuli, there is some evidence regarding schizophrenic patients’ ability to encode affect in the voice. One study by Levin, Hall, Knight, and Alpert (1985) examined verbal and vocal expression in schizophrenics, depressed patients, and a normal control group. All patients were diagnosed on the basis of Research Diagnostic Criteria (RDC), and schizophrenic patients were classified as either positive or negative symptom on the basis of a scale designed to evaluate affective adaptation (Knight, Roff, Barrnett, & Moss, 1979).
Subjects described three life events: one happy, one sad, one angry. Transcripts of selected clips from audiotape recordings of these stories were used for assessment of verbal communication. A content-filtered version of the identical clips was used for ratings of vocal affect. Volunteer judges independently rated the transcripts and the content-filtered clips on whether they expressed happy, sad, or angry affect.
Significant differences were found between groups, although all subject groups were accurate in verbal communication of affect. Positive-symptom schizophrenics were most accurate in differentiating happy, sad, and angry affect. Negative-symptom schizophrenics were less accurate in their production of vocal affect, and were particularly poor in differentiating sad and angry affect. Normal subjects were also less accurate, sounding happy in all three stories. Depressed patients were least accurate, sounding sad regardless of story condition.
Tyack and Levin (1988) extended these findings using a similar methodology. Unlike the previous study (Levin et al., 1985) patients were diagnosed according to criteria of the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–III; American Psychiatric Association, 1980), and bipolar patients were included as a psychiatric control group. In addition, subjects were asked to reexperience the target emotion before recounting happy, sad, and angry events, and to rate how they had felt while telling the stories after they finished.
The results replicated the Levin et al. (1985) study, in that schizophrenics were significantly less accurate than normal subjects in the vocal communication of all three emotions. In contrast, in verbal communication of affect, schizophrenics were accurate in communicating happiness and anger but not sadness. The reduced accuracy score for sadness appeared to be related to schizophrenics’ greater expression of sadness regardless of which story they were relating. The decreased accuracy for vocal communication of emotions in schizophrenics was not associated with a reduced ability to experience emotions, nor with the ability to express the emotions verbally. Bipolar patients did not differ significantly from either normal control subjects or schizophrenics, but were intermediate in accuracy.
These encoding studies indicate that schizophrenics are impaired in vocal communication of affect, and this is not related to an inability to express affect verbally. These results suggest that clinical findings of inappropriate or blunt affect may be due to discrepancies between schizophrenics’ verbal and vocal communications. Other channel-specific skills, such as facial expression of emotion, remain to be investigated.
In summary, visual and verbal affective processing have been shown to be impaired in schizophrenics, who are inaccurate in recognizing and labelling facial emotion. The effect of poor visuospatial skills on the perception of facial affect remains to be clarified. Schizophrenics, particularly those with negative symptoms, are also significantly impaired in conveying vocal affect. These deficits involve both encoding and decoding skills and do not appear to be associated with psychosis alone, with generalized deficit, or with an inability to experience the emotion.
Language
Several neuropsychological studies have addressed the clinical observations of abnormal speech in schizophrenics. For example, Kleist (1960) compared schizophrenic language disturbance to neurological aphasic syndromes, and argued that the former resembled Wernicke’s aphasia, which suggested a dysfunction of the left temporal lobe. Notwithstanding this and similar arguments, most investigations of elemental language functions, such as naming and repetition, find no discernible impairment in schizophrenics (Morice, 1986). Green and Walker’s (1985) observation of impaired verbal comprehension in positive-symptom schizophrenics is an exception, although the measure they use is sensitive to distractibility as well as to comprehension deficits. In general, studies of schizophrenic discourse have examined either semantic content or syntactical structure. Studies of semantic deviance reveal no obvious association with overall neuropsychological impairment as measured by LNNB and CT scans (Silverstein & Arzt, 1985). Furthermore, word-association deviance has been related to activation as a result of competition between potential responses, which suggests disinhibition and impaired executive functions rather than a disturbance of language (Chapman & Chapman, 1982).
Studies of syntax in schizophrenic language have produced mixed results, as noted by Morice (1986) in his review of linguistic studies of schizophrenics. Elemental language functions and simple syntax are reportedly intact (Andreasen & Grove, 1979; Schwarz, 1982), whereas syntactic impairment is found in complex language (Morice & McNicol, 1986). Morice postulates that the disturbance in complex language may be related to impairments of abstraction and other executive functions and may reflect a dorsolateral prefrontal dysfunction.
The question of specificity was addressed by Hoffman, Stopek, and Andreasen (1986). They compared syntactic elements of discourse in the language of schizophrenic and manic patients and found that both groups showed deficits in the coherence of overall discourse structures, but the pattern of errors differed in each group: The schizophrenics showed poor planning, and the manics demonstrated frequent loss of set, which suggests different deficits in executive functions. A subgroup of schizophrenics with affective symptoms exhibited a discourse pattern more typical of manic patients.
Crosson and Hughes (1988) proposed a comprehensive model of schizophrenic language disturbance and thought disorder that integrates cortical with subcortical functions. The model postulates two stages of production, a formulation stage and a motor programming stage. Both are coordinated by frontal systems and monitored by posterior language cortex. Specific thalamic nuclei are functionally integrated with the language cortex, whereas basal ganglia structures are integrated within the thalamo-cortical circuit. The authors attributed abnormalities in schizophrenic language production to random triggering of semantic segments and an inability to maintain contextual referents, both of which may be related to dysfunction of inhibitory circuits (from temporoparietal cortex to basal ganglia to ventral anterior nucleus to frontal language area).
In summary, there is little evidence for deficits in basic language functions in schizophrenia. The findings of linguistic studies indicate impairments in semantic content, discourse, and complex language, all of which may be secondary to cognitive deficits, and specifically to attentional and executive functions mediated by frontal-subcortical systems. This is consistent with Seidman’s (1983), Levin’s (1984a, 1984b), and Weinberger’s (1987) models, as well as with Crosson and Hughes’ (1988) specific model of language disturbances in schizophrenia.
Memory
As in the case of language disturbance, studies of memory in schizophrenia are of interest, because a finding of basic memory dysfunction would implicate pathology of brain structures involved in memory. Examination of memory functions seems particularly warranted, as several studies have documented neuropathological changes in medial limbic structures of the temporal lobe, including the hippocampus (Bogerts, Meertz, & Schonfeldt-Bausch, 1985; Kovelman & Scheibel, 1984). Investigators of memory processes in schizophrenia have focused on whether there are specific deficits in encoding versus retrieval, verbal versus visual memory, and free recall as compared with recognition memory.
Schizophrenics’ poor performance on tests of verbal memory has been demonstrated repeatedly (see reviews by Koh, 1978; Neale & Oltmanns, 1980). Calev, Venables, and Monk (1983) investigated whether this type of impairment is due to deficits at the encoding or retrieval stage of memory. Using a sorting task as an enforced orienting paradigm, they compared verbal memory performance in severely and mildly disturbed schizophrenics. Schizophrenic subjects had difficulty both sorting to criterion and recalling the sorted lists, which suggests organizational deficits. Following enforced encoding via the sorting procedure, severely and mildly disturbed schizophrenics showed different recall patterns. Mildly disturbed schizophrenics did not show a recall deficit, which indicates difficulty with encoding, whereas severely disturbed patients showed a postencoding recall deficit that the authors interpreted as similar to retrograde amnesia and suggestive of hippocampal involvement.
Other investigators also demonstrated that severity of illness and impaired verbal recall are correlated and that recall performance by schizophrenics improves with structured tasks (Calev, 1984b; Culver, Kunen, & Zinkgraft, 1986; Perlick, Stastny, Katz, Mayer, & Mattis, 1986). A differential deficit on recall as compared with recognition tasks, together with evidence for poor clustering, indicates that verbal memory deficits in schizophrenia may be related to poor organization in the encoding phase, such as impaired chunking (Calev, 1984a; Calev et al., 1983; Perlick, et al., 1986). This pattern also suggests that attention and motivation contribute to schizophrenics’ difficulty with verbal recall.
Most studies comparing verbal with visual memory in patients with schizophrenia have found comparable deficits in both modalities (Calev, Korin, Kugelmass, & Lerer, 1987; Kolb & Whishaw, 1983). The failure to find differences between verbal and visual recall implies a bilateral dysfunction, and provides further support for hippocampal involvement. These findings also argue against “gross organicity” in schizophrenics, because visual recall is typically more impaired than verbal recall in patients with diffuse brain injury (Lezak, 1983).
The specificity of memory dysfunction to schizophrenia was addressed by Sengel and Lovallo (1983), who compared paranoid and nonparanoid schizophrenics, depressives, and normal subjects on memory for a categorized word list. They found that, in an immediate recall condition, all three psychiatric groups benefitted similarly when given category cues, which suggests an organizational deficit, but that only schizophrenics showed a significant recall deficit in the delayed condition, regardless of the presence of cues. Furthermore, only schizophrenic subjects lost a number of categories in the noncued delayed condition, which suggests a more basic memory dysfunction.
A similar conclusion can be drawn from Harvey, Earle-Boyer, Wielgus, and Levinson’s (1986) study, in which both schizophrenics and bipolars showed recall that was impaired, relative to that of normal subjects, but schizophrenics’ impairment was related to encoding difficulties, whereas bipolars’ poor performance was secondary to thought disorder.
Studies of the association between memory performance and tardive dyskinesia indicate that early brain damage may predispose both schizophrenic and bipolar-disorder patients to tardive dyskinesia as well as memory deficits (Sorokin et al., 1988; Wegner et al., 1985). Only schizophrenics without tardive dyskinesia showed memory deficits whose pattern was not consistent with diffuse brain damage (Sorokin et al., 1988).
In conclusion, the memory studies indicate that there are basic verbal- and visual-recall deficits, particularly in severely disturbed schizophrenics, that are similar to retrograde amnesia and suggest bilateral hippocampal involvement. In mildly disturbed schizophrenics and bipolar patients, however, the deficits in memory are associated with organizational skills that affect encoding, and are secondary, perhaps, to a cortical attention and executive dysfunction.
Methodology
A number of methodological issues are raised by the research on neuropsychological functions in schizophrenia. One major issue is the question of generalized deficit in schizophrenia. Because schizophrenics perform poorly on many cognitive tasks, it is difficult to determine which performance deficits have etiological significance, and which are due to nonspecific, generalized factors. This distinction is especially difficult to make if performance is assessed by test scores rather than by response style and error patterns.
The variable and extended course of schizophrenic illness is also a concern in neuropsychological studies. Changes in clinical state and deterioration in function must be taken into account to determine which deficits are state- or trait-related, and this requires repeated assessment of patients over time. In any case, duration and severity of illness as well as clinical state at time of testing are important variables in the study of neuropsychological dysfunction in schizophrenia.
The identification and selection of schizophrenic subjects is a major issue, not only because of the difficulty of reaching reliable and valid diagnoses, but especially because of the heterogeneity of the disorder. Subgroups of schizophrenics classified as process/reactive, paranoid/nonparanoid, or positive/negative, for example, have unique patterns of neuropsychological impairments, as was demonstrated by Gruzelier et al. (1988).
The issue of treatment effects, and particularly of medication, electroconvulsive therapy, and hospitalization, is important to address. With respect to medication, it may be argued that many neuropsychological findings, particularly those relating to frontal attention and executive functions, may be due to treatment with neuroleptic drugs (Goldberg, 1985). Controlling for effects by testing unmedicated patients, by covariant analysis using drug dose equivalents, or by testing medicated nonschizophrenic control groups, may be useful, although none of these strategies is free of problems. Further methodological refinements—for example, using a family-study paradigm (Holzman, 1985; Matthysse & Holzman, 1987), documenting treatment history adequately, and integration of findings from neuropharmacology research—are of clear value.
Another important issue concerns the selection, administration, scoring, and interpretation of neuropsychological tests. Attempts to localize brain dysfunction in schizophrenia from neuropsychological test performance are often based on comparisons with adult neurological patients. The brain dysfunction in schizophrenia, however, is likely to be developmental, and the resulting pattern of deficits may be very different from adult onset lesions. For example, in young children, aphasia commonly occurs following right hemisphere lesions, a pattern that is completely the reverse of adult onset aphasia.
Weinberger (1987) has articulated a neurodevelopmental model of schizophrenia in which the expression of the disorder is a result of the interaction between an early fixed lesion and the maturational processes of the normal brain during young adulthood. Weinberger notes that the effects of early lesions are often not apparent until the time at which the lesioned area becomes functionally mature. As Weinberger states, the importance of this observation to schizophrenia is clear when one considers that the prefrontal cortex reaches maturity during the second and third decade of life, the age at which schizophrenia is typically diagnosed. Weinberger’s article indirectly raises the issue of comparing schizophrenics’ neuropsychological function with acutely lesioned patients, and provides a valuable heuristic for defining appropriate analogue populations for comparison studies.
An illustration of the manner in which this consideration may affect experimental design and methodology is evident in a study by Craft et al. (1987), who examined interhemispheric integration in schizophrenics with the use of a model based on callosal agenesis, a congenital disorder in which the corpus collosum fails to develop. The authors were able to demonstrate deficits that accounted for inconsistent findings by investigators who explored interhemispheric integration using adult commissurotomy as a model.
With regard to testing and scoring of neuropsychological measures, it should be noted that the standard administration procedure of some tests may fail to elicit existing deficits. For example, the organization inherent in the testing procedure may substitute for and normalize the patients’ deficits in higher cortical functions (Stuss et al., 1981). Furthermore, because poor performance can reflect different types of errors, interpretation of results based on performance levels rather than on error patterns and response styles may obscure important differences between groups (Yurgelun-Todd et al., 1988).
Future Directions
One area of interest for future investigations concerns the refinement of neuropsychological measures. Previous studies have used tests or test batteries derived from clinical neuropsychology that are often multifactorial, so that poor performance results from impairment in any one of a number of component functions (e.g., the WCST). Because of their multifactorial nature, these tests have a limited ability to measure specific cognitive deficits.
The emphasis on parsing the individual components of a given cognitive task reflects a growing interest in combining the methodologies of neuropsychology with cognitive and experimental psychology. This new field of cognitive neuropsychology is best characterized by the work of Posner and associates, for example in the area of selective attention (Posner & Presti, 1987; Posner et al., 1988). Their decomposition of visual attention into alert, interrupt, localize, disengage, move, engage, and inhibit operations has led to the successful delineation of the different neural systems involved in several of these operations, and has great potential for the study of schizophrenia, particularly if combined with the assessment of subtypes of schizophrenia and nonschizophrenic psychiatric control subjects.
Cognitive neuropsychology is made more potent by integration with dynamic imaging techniques such as Positron Emission Tomography (PET), as was demonstrated by Peterson, Fox, Posner, and Raichle (1988) in their study of visual and auditory verbal processing using a PET subtraction paradigm. Using this strategy, Peterson et al. (1988) provided evidence for a parallel processing model of auditory and visual word recognition, as opposed to the serial processing model assumed in neurological theories of word recognition. Applied to neuropsychological tests, such as the WCST, the combined methodologies of function parsing and PET subtraction could imbue neuropsychological investigations of schizophrenia with added rigor and power.
Summary
Evidence for brain dysfunction in schizophrenia, derived from neurophysiological, biochemical, and structural studies of the schizophrenic brain (Snyder, 1982; Stevens, 1982; Weinberger et al., 1983), has led to several models for this dysfunction (Gruzelier et al., 1988; Levin, 1984a, 1984b; Seidman, 1983; Walker & McGuire, 1982; Weinberger, 1987). Neuropsychological paradigms, limited in the past to attempts to rule out organicity, have recently been used to describe the possible nature of this brain dysfunction, yielding data in support of some of these models.
Studies of attention reveal that schizophrenic patients display attentional deficits that vary according to several clinical dimensions, including severity of illness. Nonparanoid and negative-symptom schizophrenics perform more poorly on tests of attention than do paranoid or positive-symptom patients. Qualitative analysis indicates that positive-symptom patients display more intrusions than do negative-symptom patients. These findings are consistent with the Seidman (1983), Mirsky (1988), and Levin (1984a, 1984b) models of frontal-subcortical modulation of attention. In addition, studies of selective visual attention have provided some support for a lateralized left hemisphere deficit (Posner et al., 1988).
Similar support for these models is provided by findings of impaired executive functions. Schizophrenics are consistently impaired on tests with demonstrated sensitivity to frontal lesions. Despite the presence of confounding factors, it is clear that a subgroup of schizophrenic patients have significant difficulties completing tasks that require abstraction, sustained attention, set shifting, inhibition of irrelevant stimuli, planning, and self-regulation. Some of these deficits are seen in bipolar patients, so the question of specificity remains open—although the evidence presented thus far suggests that schizophrenic and bipolar patients exhibit different processing deficits in executive functions.
Studies on psychomotility in schizophrenia indicate a slowed motor response that is not a byproduct of, though it is related to, cognitive-attentional functions. Studies of motor laterality and handedness have yielded inconsistent results, leaving the question of hemispheric differences in schizophrenia open for further investigation. Issues of specificity and heterogeneity require further clarification. Nevertheless, this domain of research also supports the Seidman (1983) and Levin (1984a, 1984b) models, although the evidence for the Walker and McGuire (1982) model is less clear.
The visuoconstructional deficits that have been identified in a subset of patients are consistent not with impairments of primary visuoperceptual processes, but rather with organizational and executive dysfunction; this suggests an involvement of right frontal regions.
The role of visuoperceptual deficits in decoding facial affect is yet to be adequately tested. However, the evidence suggests that schizophrenics have a specific deficit in recognizing and verbally labelling facial emotion. Encoding deficits, namely poor expression of affect in the voice, are especially likely to be found in negative-symptom schizophrenics and give further indication of a primary impairment of affect. Although this is consistent with right hemisphere dysfunction, the research on affect in schizophrenia is too preliminary to warrant conclusions regarding the localization of these deficits.
Studies of language functions have documented impairments in verbal comprehension and the use of complex syntax, which suggests problems with abstraction or attention. There is little evidence of impairments of basic language functions.
Investigations of memory have identified deficits in both visual and verbal memory; this suggests that diffuse brain damage, which is characterized by greater visual than verbal memory dysfunction, is not the basis of memory impairment in all schizophrenics. Mildly disturbed patients are more impaired in encoding than in retrieving information; this indicates poor organization of information and possibly poor attention. Patients with severe symptoms, however, also demonstrate retrograde amnesia, which suggests a primary dysfunction of memory involving medial limbic areas. This is consistent with the Seidman (1983) and Levin (1984a, 1984b) models, as well as with morphometric studies (Bogerts et al., 1985).
In conclusion, neuropsychological studies have provided valuable insights into brain dysfunction in schizophrenia. Although there are limitations to interpretations of clinical neuropsychological research, the introduction of qualitative analysis, the parsing of multifactorial tasks, and the refinement in clinical assessment offer solutions to some of these limitations and provide useful information regarding the neuropsychology of schizophrenia. The integration of such complementary fields as cognitive psychology and neurobiology promises to elucidate further brain–behavior relationships in schizophrenia, and moves us closer to a true understanding of this complex disorder.