The stability of neuropsychological performance in schizophrenia and its relationship to clinical change was contrasted between 60 patients with schizophrenia (30 first-episode, 30 previously treated) and 38 healthy controls using a comprehensive neuropsychological battery and clinical scales administered at intake and at a 19-month follow-up. Consistent with the neurodevelopmental model of schizophrenia, patients demonstrated deficits in cognitive performance at initial testing and did not show decline at follow-up. There were no differences in neuropsychological performance over time between first-episode and previously treated patients, nor between male and female patients or controls. As expected, patients improved clinically with treatment with respect to both positive and negative symptoms. First-episode patients improved more on the positive symptoms of hallucination and delusion; male and female patients showed equivalent clinical improvement. Clinical improvement correlated positively with neuropsychological change, with improved negative symptomatology accounting for most of the significant correlations.

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Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 15 O-water measures of rCBF. Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals.Schizophrenia was previously thought of primarily as a frontal lobe disorder. Central to this model were neuropsychological results of impaired Wisconsin Card Sorting Test (WCST; Berg, 1948;Grant & Berg, 1948) performance (Goldberg, Weinberger, Berman, Pliskin, & Podd, 1987) and cerebral blood flow (CBF) findings of "hypofrontality" at rest (Ingvar & Franzen, 1974) and in response to WCST task demands (Weinberger, Berman, & Zee, 1986). An alternative model proposed that schizophrenia primarily affects temporal lobe function. Support for this theory included neuropsychological results of differentially impaired learning and memory (Saykin et al., 1991), functional imaging evidence of resting left temporal lobe hypermetabolism , and atypical midtemporal CBF asymmetries in response to memory task demands (Gur, Jaggi, Shtasel, Ragland, & Gur, 1994).Copyright 1998 by the American Psychological Association, Inc.Correspondence concerning this article should be addressed to: J. Daniel Ragland, 10th Floor Gates Building/HUP, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104. ragland@bblmail.psycha.upenn.edu. J. Daniel Ragland, Ruben C. Gur, David C. Glahn, David M. Censits, Mark G. Lazarev, and Raquel E. Gur, Department of Psychiatry, University of Pennsylvania Health Systems; Robin J. Smith and Abass Alavi, Department of Radiology, University of Pennsylvania Health Systems. HHS Public Access Author manuscriptNeuropsychology. Author manuscript; available in PMC 2015 May 21. Published in final edited form as:Neuropsychology. 1998 July ; 12(3): 399-413. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptMore recently, researchers have begun to acknowledge the reciprocal interconnectivity of the prefrontal cortex with the hippocampus (Goldman-Rakic, Selem...

Whereas verbal learning has received considerable attention by cognitive neuropsychology, spatial object learning has been more resistant to study. The paucity of visual learning data has hampered attempts to clarify if visual learning has unique features with specialized neural substrates. In schizophrenia, severe verbal learning impairment has been established, but lack of comparable visual learning measures has thwarted the dissociation of verbal and visual abilities. The Visual Object Learning Test (VOLT) was developed to examine aspects of visual-spatial learning and memory in a manner analogous to available verbal tests. Studies were performed to establish normative performance characteristics, convergent and divergent validity, and the sensitivity of the VOLT to detection of individual differences in normal (through sex and age) and pathologic variability (through persons with schizophrenia). The results indicated excellent internal consistency, convergent and divergent validity, and sensitivity to the effects of aging and pathology. Persons with schizophrenia were impaired in both learning and retention. The authors conclude that memory impairment in schizophrenia may not be specific to verbal learning.

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.