Abnormal Studies

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Authors

Andreasen NC. O'Leary DS. Flaum M. Nopoulos P. Watkins

GL. Boles Ponto LL. Hichwa RD.

Institution

Mental Health Clinical Research Centre, University of Iowa College of Medicine, Iowa City, USA.

Title

Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naive patients.

Source

Lancet. 349(9067):1730-4, 1997 Jun 14.

Abstract

BACKGROUND: There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET). METHODS: We studied 17 neuroleptic-naive patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. FINDINGS: An initial omnibus test with a randomisation analysis indicated that patients differed from normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital, medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits. INTERPRETATION: These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.

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Authors

Andreasen NC. O'Leary DS. Cizadlo T. Arndt S. Rezai K.

Ponto LL. Watkins GL. Hichwa RD.

Institution

Mental Health Clinical Research Center, University of Iowa College of

Medicine and Hospitals and Clinics, Iowa City 52242, USA.

Title

Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry.

Source

Proceedings of the National Academy of Sciences of the United States of

America. 93(18):9985-90, 1996 Sep 3.

Abstract

Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a "cognitive dysmetria" due to dysfunctional prefrontal-thalamic-cerebellar circuitry.

Authors

O'Leary DS. Andreasen NC. Hurtig RR. Kesler ML. Rogers M. Arndt S.

Cizadlo T. Watkins GL. Ponto LL.

Kirchner PT. Hichwa RD.

Institution

Mental Health Clinical Research Center, University of Iowa Hospitals and Clinics, Iowa City, USA.

Title

Auditory attentional deficits in patients with schizophrenia. A positron emission tomography study.

Source

Archives of General Psychiatry. 53(7):633-41, 1996 Jul.

Abstract

BACKGROUND: Patients with schizophrenia have frequently been found to perform poorly on tasks requiring selective attention, defined as the ability to focus attention on relevant information while simultaneously ignoring irrelevant stimuli. This study explores the brain mechanisms mediating attentional processing in patients with schizophrenia by measuring their regional cerebral blood flow (rCBF) with positron emission tomography using [15O] water as they performed tasks that differed systematically in attentional demand. METHODS: Ten schizophrenic patients (either neurolepticnaive or withdrawn from medication) (patient group) and 10 normal volunteers (control group) performed auditory target detection tasks. Different types of auditory stimuli (environmental sounds, meaningless speech sounds, and words) were presented either binaurally (ie, same sounds in both ears) or dichotically (simultaneous and different sounds in the 2 ears). In dichotic conditions, subjects were instructed to focus on either their left or right ear. RESULTS: Initial subtraction-based image analyses sought significant rCBF changes anywhere in the brain. Patients consistently had less significant activation than controls in right superotemporal gyrus (STG). Follow-up analyses used regions of interest traced on individual magnetic resonance images to precisely measure rCBF in STG. Unlike controls, patients had higher rCBF in the left STG during all activation conditions. CONCLUSIONS: The abnormal task-related rCBF asymmetry in STG of schizophrenic patients may indicate an isolated temporal lobe deficit, but it may also indicate abnormality in the thalamocortical circuitry mediating selective attention and/or in the brain systems that integrate auditory processing in the 2 hemispheres.

Authors

Giordani B. Berent S. Boivin MJ. Penney JB. Lehtinen S. Markel DS.

Hollingsworth Z. Butterbaugh G. Hichwa RD. Gusella JF.

et al.

Institution

Department of Psychiatry, University of Michigan, Ann Arbor.

Title

Longitudinal neuropsychological and genetic linkage analysis of persons at risk for Huntington's disease.

Source

Archives of Neurology. 52(1):59-64, 1995 Jan.

Abstract

OBJECTIVE: To determine (1) whether the neuropsychological profiles of healthy individuals at risk (AR) for Huntington's disease who were positive (AR/+) or negative (AR/-) for the Huntington's disease genetic marker differed from those of symptomatic patients with Huntington's disease and normal control individuals and (2) whether the neuropsychological performance of the two AR groups differed from each other on three assessments during a 4-year span. DESIGN: Case-control, double-blind study, with AR status determined by genetic linkage analysis (G8 probe), in addition to examination of trinucleotide repeats for most AR subjects. SETTING: The Neuropsychology Program in the Department of Psychiatry and the Department of Neurology at the University of Michigan Medical Center, Ann Arbor, a tertiary care center. PARTICIPANTS: Eight subjects matched as closely as possible for age, gender, and education in each of the following groups: AR/+, AR/-, normal control, and Huntington's disease. MEASURES: A battery of neuropsychological tasks, including measures of intelligence, memory, problem solving, and motor ability. RESULTS: Although both AR groups demonstrated variability on select intellectual subtests relative to normal subjects, they did not differ from each other on the three assessments during a 4-year span. Patients with Huntington's disease performed more poorly than the other groups across a range of neuropsychological measures. CONCLUSIONS: These results do not support previous evaluations concluding that AR/+ individuals demonstrate cognitive impairments as compared with AR/- individuals. Findings in earlier studies without genetic linkage analysis of lower performance of AR individuals, including children, as compared with normal controls may relate to extraneous environmental and familial issues that interfere with intellectual development.