The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.

The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography.

A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum.

Regional cerebral blood flow and cognitive function in Huntington's disease and schizophrenia. A comparison of patients matched for performance on a prefrontal-type task.

Matching patients with etiologically distinct but clinically overlapping cognitive disorders on performance of a regionally specific neuropsychological task is a novel and potentially powerful approach to highlighting differences in the pathophysiological mechanisms of impaired cognition. We used this strategy to compare patients with Huntington's disease (HD) and schizophrenia (SC), disorders that share similarities in cognitive impairment. Patients were matched on the basis of performance on the Wisconsin Card Sorting test of "prefrontal" function, after which neuropsychological test data and regional cerebral blood flow data were determined while patients who performed the Wisconsin Card Sorting test were examined.

Lateralisation of cortical function during cognitive tasks: regional cerebral blood flow studies of normal individuals and patients with schizophrenia.

To assess cognitively-related regional asymmetries of brain function, regional cerebral blood flow (rCBF) was determined by the xenon inhalation method while normal subjects performed 10 different tasks and also while they were at rest. In addition to healthy subjects, patients with schizophrenia were also studied. A total of 447 rCBF studies were carried out during the following conditions: the Wisconsin Card Sort Test, a numbers matching test, a symbols matching test, Raven's Progressive Matrices, an auditory discrimination test, an auditory control task, two versions of a visual continuous performance task, line orientation, semantic classification, and resting.

Behavioral and electroencephalographic effects of the adenosine1 agonist, L-PIA.

The effects of N6-(L-2-phenylisopropyl)-adenosine (L-PIA), an A1 agonist, were measured on both spontaneous locomotor activity and electroencephalographic (EEG) measures of sleep in rats. L-PIA strongly inhibited motor activity at 100 micrograms/kg intraperitoneally (IP), a dose which had no statistically significant effects on EEG-defined sleep. A higher dose of L-PIA (200 micrograms/kg) increased the latency to sleep initiation and inhibited later REM sleep.

Anxiety and cerebral blood flow during behavioral challenge. Dissociation of central from peripheral and subjective measures.

To investigate the relationship between anxiety and regional cerebral blood flow, we administered behavioral challenges to 10 patients with obsessive-compulsive disorder while measuring regional cerebral blood flow with the xenon 133 inhalation technique. Each patient was studied under three conditions: relaxation, imaginal flooding, and in vivo (actual) exposure to the phobic stimulus. Subjective anxiety, obsessive-compulsive ratings, and autonomic measures (heart rate, blood pressure) increased significantly, but respiratory rate and PCO2 did not change across the three conditions.

Recall memory deficit in schizophrenia. A possible manifestation of prefrontal dysfunction.

Patients with schizophrenia have memory deficits when compared to other neuropsychiatric and normal samples, but the mechanism by which the deficits arise is obscure. In the present study, 13 older, less educated normal subjects, and 31 inpatients with schizophrenia were administered the Selective Reminding test. In addition, the schizophrenic patients received the Mini Mental State Exam and the Brief Psychiatric Rating Scale.

The effect of apomorphine on regional cerebral blood flow in schizophrenia.

A double-blind, placebo-controlled crossover study of the effects of apomorphine on regional cerebral blood flow (rCBF) during a prefrontal cortex activation task was undertaken to explore the role of dopamine on cortical function. The subjects were eight drug-free, chronically psychotic patients; six patients had schizophrenia. In each, apomorphine increased the relative prefrontal flow.

Met5-enkephalin-Arg6-Gly7-Leu8 immunoreactivity in rat and human cerebrospinal fluid: influence of neuroleptic drugs and electroconvulsive shock.

Met5-Enkephalin-Arg6-Gly7-Leu8 immunoreactivity was quantitated in both rat and human cerebrospinal fluid (CSF) by radioimmunoassay with a carboxy-terminal directed antiserum. The immunoreactivity in CSF was chromatographically characterized in both species and was found to consist almost exclusively of high molecular weight forms. In human CSF there was approximately 300 fmol/ml and in the rat 1,500 fmol/ml of immunoreactivity.

Performance of schizophrenic patients on putative neuropsychological tests of frontal lobe function.

Though individual tests thought to assess frontal lobe function have been administered to patients with schizophrenia for many years, approaches in which a number of tests thought to tap a single function or brain region have rarely been used. Such an approach might define a critical test or a common dysfunctional cognitive process. In the present study four putative neuropsychological tests of frontal lobe integrity, namely, the Wisconsin Card Sorting Test, the Category Test, Trail Making B, and verbal fluency, were administered to 28 patients with schizophrenia.

Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV. Further evidence for regional and behavioral specificity.

In previous studies we found that patients with chronic schizophrenia had lower regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) than did normal subjects during performance of the Wisconsin Card Sort Test, an abstract reasoning task linked to DLPFC function. This was not the case during less complex tasks. To examine further whether this finding represented regionally circumscribed pathophysiology or a more general correlate of abstract cognition, 24 medication-free patients and 25 age- and sex-matched normal control subjects underwent rCBF measurements with the xenon 133 technique while they performed two tasks: Raven's Progressive Matrices (RPM) and an active baseline control task.

Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. III. A new cohort and evidence for a monoaminergic mechanism.

We previously reported that compared with normals, patients with chronic schizophrenia have reduced regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) during performance of the Wisconsin Card Sort Test (WCS), a DLPFC-related cognitive task, but not during nonprefrontal tasks, such as a simple number-matching (NM) test. We also found that unlike normals, patients failed to activate DLPFC during the WCS over their own baseline (NM) level. To explore the reproducibility of these findings, a new cohort of 16 medication-free patients underwent a series of xenon 133 inhalation rCBF studies under the following conditions: at rest, while performing the WCS, and while performing NM.

Early experience of health maintenance organizations under Medicare competition demonstrations.

Between 1982 and 1985, health maintenance organizations (HMO's) entered the Medicare market under the Medicare competition demonstrations. The status and experience of these HMO's, their market areas,, and the benefit packages they offered are presented. Information from case studies of 20 of these HMO's is used to discuss the planning process through which the organizations prepared to enter the Medicare market.

Speculation on the meaning of cerebral metabolic hypofrontality in schizophrenia.

Cerebral metabolic hypofrontality in schizophrenia is a controversial research finding. In this article we discuss some of the issues that fuel this controversy, and we speculate on the neural mechanisms that may be responsible for the finding. Most regional cerebral blood flow (rCBF) studies using radioactive xenon have found hypofrontality; the results of positron emission tomography (PET) studies have been less consistent.

Mesocortical dopaminergic function and human cognition.

In summary, we have reviewed rCBF data in humans that suggest that mesoprefrontal dopaminergic activity is involved in human cognition. In patients with Parkinson's disease and possibly in patients with schizophrenia, prefrontal physiological activation during a cognitive task that appears to depend on prefrontal neural systems correlates positively with cognitive performance on the task and with clinical signs of dopaminergic function. It may be possible in the future to examine prefrontal dopamine metabolism directly during prefrontal cognition using positron emission tomography and tracers such as F-18 DOPA.

Prefrontal cortical blood flow and cognitive function in Huntington's disease.

To examine the relationship between cortical physiology and dementia in Huntington's disease, rCBF during three different behavioural conditions, one of which emphasised prefrontal cognition, was determined by xenon-133 inhalation in 14 patients with Huntington's disease and in matched controls. Cortical rCBF was not reduced in Huntington's disease patients even while they manifested overt prefrontal-type cognitive deficits. Caudate atrophy on CT and rCBF were significantly correlated, but only during the prefrontal behaviour where the correlation was positive.

Regional cerebral blood flow in severe developmental dyslexia.

Regional cerebral blood flow was measured under three task conditions in 14 men with severe developmental dyslexia and their control subjects using a xenon 133 inhalation technique. No group differences in overall level or in pattern of gray matter flow were seen under relatively undemanding cognitive conditions. Despite minimal group differences in performance, the dyslexic group showed an increased hemispheric asymmetry (left greater than right) on a semantic classification task and a reduced anteroposterior difference on a line orientation task relative to controls.

Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test.

Recent physiological and cognitive studies of schizophrenia have implicated dysfunction of prefrontal cortex as a possible explanation for some of the disabling intellectual and social aspects of the disorder. To investigate the potential reversibility of cognitive deficits and the role of state variables, eg, attention and motivation, three groups of patients with schizophrenia were administered the Wisconsin Card Sorting Test on six consecutive occasions. Two of the groups received incremental information on how to do the test, including explicit card-by-card instruction.

Cortical "stress tests" in schizophrenia: regional cerebral blood flow studies.

A total of 261 regional cerebral blood flow (rCBF) studies were carried out on 34 medication-free patients with chronic schizophrenia and 50 normal subjects. rCBF, an indicator of local cortical metabolism and activity, was measured during the resting state and also during four cognitive activation tasks or "cortical stress tests." The latter included the Wisconsin Card Sort (WCS), a test of prefrontal lobe function; a simple numbers matching task, and two versions of a visual Continuous Performance Task (CPT).

A relationship between anatomical and physiological brain pathology in schizophrenia: lateral cerebral ventricular size predicts cortical blood flow.

The authors studied the relationship between lateral cerebral ventricular size and regional cerebral blood flow during mental activation in 30 patients with schizophrenia. Patients with large ventricles had diffusely lower cortical gray matter blood flow than patients with small ventricles. In addition, an inverse correlation between ventricular size and prefrontal blood flow was observed while patients were attempting to solve a neuropsychological test specifically related to the prefrontal cortex.

HMOs in the Medicare market. Part 1.

Final governmental regulations permitting all qualified health maintenance organizations and competitive medical plans to enter the Medicare market were published early last year. This action has created a significant need for information on marketing strategies and operational issues pertaining to this new area. Mathematica Policy Research was awarded a grant by HCFA to evaluate the Medicare Competition Demonstration program undertaken by 26 HMOs and CMPs between August 1982 and December 1984, with a focus on the marketing strategies and operational decisions and changes during the initial period of entering the Medicare market.

A multidisciplinary patient education workshop to integrate staff training with program development.

A four session multidisciplinary workshop was held to teach Veterans Administration (VA) Medical Center staff basic patient education design principles. During the sessions, staff, working in teams, designed patient education programs on a wide variety of health care topics. Guidance to teams was provided at each step of program development so that at the end of the workshop, programs were ready for implementation.