Schizophrenia and the frontal brain: a quantitative review.

Structural and physiological frontal brain system deficits in patients with schizophrenia are reviewed quantitatively. We report effect sizes from studies since 1980 that used structural (CT, MRI), and functional (PET) neuroimaging methods. We found both literatures to be distinguished by heterogeneity whereby most patients show normative frontal function and structure, a minority shows diminished values and some patients demonstrate augmented function and structure rather than deficit. The average magnitude of difference between patients and controls is generally too modest to support the idea that frontal brain dysfunction is a necessary component of schizophrenia. This modesty is most apparent in average effects obtained for frontal brain volume (M = -.36), left frontal brain volume (M = -.16), frontal resting metabolism, and blood flow (M = -.64). Effect sizes of this magnitude imply that schizophrenia and control distributions overlap by as much as 88% and no less than about 60% on frontal brain measures. It is only when behavioral measures are employed as activation tasks during frontal blood flow and metabolism studies, that average effect sizes rise in magnitude to indicate patient-control distribution overlaps that are less than 50%. Overall, the findings are hard to incorporate within single disease models that propose major involvement of the frontal system, at least at the degree of resolution obtained with current imaging technology.

Neurocognitive deficit in schizophrenia: a quantitative review of the evidence.

The neurocognitive literature on test performance in schizophrenia is reviewed quantitatively. The authors report 22 mean effect sizes from 204 studies to index schizophrenia versus control differences in global and selective verbal memory, nonverbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language, and interhemispheric tactile-transfer test performance. Moderate to large raw effect sizes (d > .60) were obtained for all 22 neurocognitive test variables, and none of the associated confidence intervals included zero. The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.

Parsing schizophrenia with neurocognitive tests: evidence of stability and validity.

The stability and validity of a neurocognitive typology for schizophrenia were studied in 55 chronic patients who met DSMIII-R criteria for the illness. Subtypes were based on an earlier cluster analytic study by Heinrichs and Awad (1993) that utilized the following variables: IQ (WAIS-R), categories (Wisconsin Card Sorting Test), free recall intrusions (California Verbal Learning Test), and bilateral motor performance (Purdue Pegboard). Stability was examined by analyzing subtype assignment at the original assessment and 3 years later at follow-up. Stability over this interval was variable with an overall kappa of .45 and individual kappas from .12 to .66. Adjunct cognitive and clinical data gathered at follow-up provide evidence for the validity of several subtypes, especially in terms of their cognitive and functional differences. There was no evidence of symptom differences in this relatively asymptomatic medicated sample of patients. The results are discussed in terms of the possibility that several patterns of neurocognitive dysfunction may underlie schizophrenia, with implications for understanding the heterogeneity of the illness and its variable functional outcomes.

Performance on tests of diencephalic-hippocampal verbal memory function in schizophrenia, Korsakoff's syndrome and personality disorder.

Performance on selected scores from the California Verbal Learning Test (CVLT) was compared in schizophrenia, Korsakoff's syndrome, and personality disorder patients. Five CVLT scores sensitive to dysfunction in the diencephalic-hippocampal memory system and one attention-sensitive variable were examined. The patient groups were matched on age, education, and verbal ability (WAIS-R). Schizophrenia patients differed consistently from Korsakoff patients on diencephalic-hippocampal memory variables. However, they did not differ significantly from patients with personality disorders. The three groups were comparable on immediate memory. Results are discussed in terms of the nature of memory problems in schizophrenia and the extent to which these problems reflect dysfunctional subcortical processing.

Schizophrenia and the brain. Conditions for a neuropsychology of madness.

In this article I describe 3 conditions for understanding schizophrenia as a kind of brain disease. First, the disorder must cohere as a clinical entity that is distinct from other disorders. Second, schizophrenia must be linked with an identifiable neuropathology. Third, implicated brain systems must have behavioral functions that fit the psychological characteristics actually seen in schizophrenia. In each case, the evidence is weak or equivocal. However, this does not mean that neurogenic interpretations are untenable. Instead, the primacy of problems associated with the first condition, the need to parse schizophrenia and reduce heterogeneity, must be recognized. Progress in understanding schizophrenia depends on a neurobehavioral approach to resolving the heterogeneity problem.

Neurocognitive subtypes of chronic schizophrenia.

Performance on four key neurocognitive tasks was used to search for subtypes in 104 DSM-IIIR schizophrenic patients. The tasks were the Wisconsin Card Sorting Test to index executive prefrontal cerebral function, intrusion errors from the California Verbal Learning Test to tap hippocampal-diencephalic mnestic function, bilateral hand performance on the Purdue Pegboard to index fine motor-basal ganglial function, and a pro-rated IQ from the Wechsler Adult Intelligence Scale-Revised to measure general cognitive-cerebral function. Neurocognitive data were analyzed using hierarchical and disjoint clustering procedures with Euclidean distance. A five cluster solution was considered optimal. Cluster 1 (n = 24) comprised patients with selective executive-prefrontal dysfunction; cluster 2 (n = 16) suggested normative function; cluster 3 (n = 20) involved patients with executive-motor/cortico-basal ganglial deficit; cluster 4 (n = 25) suggested dementia/multi-focal disturbance; and cluster 5 (n = 19) consisted of patients with selective motor-basal ganglial deficit. The subtypes differed significantly in age, duration of illness, and extent of hospitalization. Suggestive trends in sex composition and anti-Parkinsonian medication patterns were noted. Neurocognitive tasks combined with cluster analysis have promise in reducing and clarifying the heterogeneity of schizophrenia.

Selected neurocognitive test data and work attendance for chronic psychiatric patients.

The relationship between work attendance-absence and selected measures of executive (Wisconsin Card Sorting Test, Trail Making B) and motor (Purdue Pegboard) function was explored in a sample of 42 chronic psychiatric patients at a sheltered workshop setting. Work attendance was unrelated to intelligence but correlated with several executive and motor variables. A stepwise regression analysis produced a three-variable model which accounted for 40% of the variance. However, the direction of the relationships suggested that high attendance was most likely for older, more cognitively rigid patients, with less manual dexterity than other patients. These findings are discussed in terms of the need to consider jointly neurocognitive and environmental constraints on ecological functioning.

Copying strategies and memory on the Complex Figure Test in psychiatric patients.

We assessed three copying strategies on the Rey-Osterrieth Complex Figure Test among 50 psychiatric patients. The strategies were featural (detail-focused), contextual (framework-focused), and mixed. Reliable classification of each patient's copying strategy showed 7 patients used a featural and 7 patients used a contextual strategy. The remaining 36 used a mixed strategy involving both elements. Analysis indicated that patients who met DSM-III-R criteria for schizophrenia tended to use a mixed strategy. Nonschizophrenic patients also favoured the mixed approach. Moreover, when subjects were divided into groups based on their strategies, there were no differences in copying accuracy. However, the groups differed on immediate and delayed recall of the Complex Figure Test. Patients who adopted a featural strategy on the copy trial had the lowest recall scores. "Process" variables may be important in understanding neurocognitive functioning in schizophrenia; however, there is little evidence that schizophrenic patients use copying strategies consistent with lateralized impairment of brain function.

Relationship between neuropsychological data and response to behavioral treatment in a case of carbon monoxide toxicity and dementia.

The ability of learning measures to predict a behavioral treatment response was of interest in this study. A severely impaired and behaviorally disturbed female neuropsychiatric patient was unable to demonstrate any learning on "direct" tests involving multiple free recall trials or cued paired associate recall. However, she performed normally on an "indirect" test involving implicit learning of new associations. To assess whether direct or indirect measures tapped the kind of learning required by a positive reinforcement-based treatment approach, a token program was carried out. There was a 72.5% reduction in maladaptive behavior relative to baseline, indicating a positive treatment response. The results are discussed in terms of the potential treatment utility and predictive validity of indirect measures of learning and memory and the relation of neuropsychological data to intervention issues in general.

Neuropsychological test performance and employment status in patients referred for assessment.

A summary index of neuropsychological impairment (mean Luria-Nebraska T score), along with age, education, and presence/absence of confirmed brain disease, was used to predict employment status (working/not working). Subjects were 50 patients referred for neuropsychological assessment of confirmed or suspected brain damage. The Luria-Nebraska index contributed about 8% of explained variance independently of the other predictors. The joint validity was about 29% of criterion variance. This is related to issues in the use of neuropsychological data to predict functional variables.

Attempted clinical application of a technique for promoting robust free recall to a case of alcoholic Korsakoff's syndrome.

A case study is reported which attempted to teach personal orienting information (i.e., recent history) to an amnesic male patient. The structured cuing methods reported by Kovner, Mattis, and Pass (1985, Journal of Clinical and Experimental Neuropsychology, 7, 395-411) were adopted. This involves structured presentation and cuing of target words embedded in a narrative. Some patients eventually are able to freely recall large amounts of material presented in this way. In the present case, the patient received 30 training sessions over 8 weeks. The material to be remembered was 10 target words pertaining to recent personal history. These words were embedded in accompanying storyline. The patient's immediate recall at the end of each session improved to some extent over the training period. However, delayed recall for the material remained nil throughout. Twelve months after the last training session the patient showed some "implicit" retention of the material. The findings are contrasted with Kovner et al.'s dramatic results and discussed.

Frontal cerebral lesions and violent incidents in chronic neuropsychiatric patients.

The contribution of selected neurological, psychiatric, and demographic variables to the frequency of violent incidents was studied in an institutional context. A multiple regression procedure was used to predict the number of documented incidents for each of 45 neuropsychiatric patients. This procedure yielded a 5-variable equation that accounted for close to a third of the variance. The first three variables entered each contributed uniquely to validity. These variables were presence of focal frontal cerebral lesions, number of inpatient days, and history of seizure disorder. The presence of cerebral damage in general did not predict violent incidents. The results are discussed in terms of possible brain-behavior relationships and the nature of the patient population.

Frequency of occurrence of a WAIS dementia profile in male head trauma patients.

This study investigated Fuld's (1983) contention that a WAIS dementia profile occurs infrequently in conditions other than Alzheimer's Disease. A sample of 50 male head trauma patients was examined for incidence of the profile. The WAIS profile occurred in five cases (10%) of the patients. This compares favourably with the figures reported for patients with multiple infarcts and is consistent with Fuld's position.

Does depression in patients with known or suspected cerebral disease contribute to impairment on the Luria-Nebraska Neuropsychological Battery?

Both the Luria-Nebraska Neuropsychological Battery (LNNB) and the Beck Depression Inventory (BDI) were administered to 48 consecutively referred patients. These consecutively seen patients comprised 25 cases of confirmed brain damage and 23 cases of "suspected" or questionable damage. Product-moment correlations were calculated between the BDI and three LNNB-derived indices of impairment. No relationship was found between depression and any of the LNNB performance indicators, indicating that the battery may be robust in the presence of depression. Necessary constraints on this implication were discussed and explicated in light of the concurrent need to evaluate new neuropsychological instruments in realistic clinical contexts.

Verbal responses of male college students to human figure paintings varying in collative properties, perceived sexuality, and perceived aggression.

20 male undergraduates rated 60 human figure paintings on verbal scales to index collative variability (e.g., simple-complex), perceived sexuality, and perceived aggression in the stimuli. Regression equations were used to predict epistemic (interest) and diversive (pleasingness) responses to the paintings. Collative variability predicted diversive but not epistemic appreciation. Perceived aggression was the strongest predictor for both types of aesthetic reaction. Perceived sexuality was most strongly related to diversive appreciation. Both linear and nonlinear functions emerged and these were discussed in terms of consistency with Berlyne's 1971 theory of aesthetics.