John M. Morihisa

Positron emission tomography in schizophrenic patients with and without neuroleptic medication

Positron emission tomography using [18F]2-fluoro-2-deoxy-d-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradients.

Dysfunction in a prefrontal substrate of sustained attention in schizophrenia

Regional brain metabolism was measured in normal subjects and patients with schizophrenia while they performed an auditory discrimination task designed to emphasize sustained attention. A direct relationship was found in the normal subjects between metabolic rate in the middle prefrontal cortex and accuracy of performance. The metabolic rate in the middle prefrontal cortex of patients with schizophrenia, even those who performed as well as normals, was found to be significantly lower than normal and unrelated to performance. The findings point to a role of the mid-prefrontal region in sustained attention and to dysfunction of this region in schizophrenia.

Increased temporal lobe glucose use in chronic schizophrenic patients.

Temporal lobe glucose metabolic rate was assessed in 21 off-medication patients with schizophrenia and 19 normal controls by positron emission tomography with 18F-deoxyglucose. Patients with schizophrenia had significantly greater metabolic activity in the left than the right anterior temporal lobe, and the extent of this lateralization was in proportion to the severity of psychopathology.

Adrènal medulla grafts survice and exhibit catecholamine-specific fluorescence in the primate brain

Parkinsons disease most consistently involves pathologic changes in the substantia nigra, which is the major source of dopamine to the striatum. It has been shown that either fetal substantia nigra or adrenal medulla tissue implanted into the rat brain survives, produces dopamine, and improves behavioral abnormalities induced by deprivation of the caudate nucleus of its dopaminergic innervation. Thus, catecholamine-containing grafts could be potential replacements for destroyed or damaged dopaminergic neurons in patients with Parkinsons disease. To explore the potential of this therapeutic approach, fetal substantia nigra or host adrenal medulla were grafted to the denervated caudate nucleus of the rhesus monkey. Under the specific conditions of our experiment, fetal substantia nigra did not survive in either of two animals tested. On the other hand, some tissue from adrenal medulla grafts survived in all four animals tested. These grafted cells contained catecholamines, as indicated by the presence of specific glyoxylic acid-induced catecholamine fluorescence. In two of the four animals, however, the grafts contained fewer than 10 surviving cells, and in the other two animals, about 190 and 300 cells were found, respectively. Despite the small numbers of cells, this is the first demonstration that peripheral tissue autografts can survive implantation into the nonhuman primate central nervous system.

Catecholamine content of intracerebral adrenal medulla grafts

The rotational behavior which is produced by substantia nigra lesions can be decreased by adrenal medulla grafts adjacent to the denervated striatum. Perhaps these grafts secrete dopamine that diffuses into the striatum. In the present study, we measured concentrations of catecholamines in adrenal medulla grafts as compared with the normal adrenal medulla. The grafts were found to have high but extremely variable concentrations of dopamine. In hosts with substantia nigra lesions, concentrations of dopamine in the adrenal medulla grafts were decreased. Substantia nigra lesions, however, tended to increase concentrations of epinephrine in the grafts, while norepinephrine and total catecholamine concentrations were not significantly affected. It is concluded that at least some adrenal medulla grafts contain concentrations of dopamine sufficient to account for their behavioral effects.

The alcohol facilitation effect on memory: A dose-response study

Sixteen normal male subjects participated in four sessions where they studied a set of pictures followed by either placebo, 0.025, 0.50, or 1.0 ml/kg alcohol. Later, when sober, recognition memory was tested. These doses resulted in peak blood alcohol concentrations (BAC) of 0.00, 0.018, 0.034, and 0.067 g/100 ml, respectively. The 1.0 and 0.50 ml/kg doses significantly improved memory for pictures studied before drinking. Alcohol appears to enhance memory directly rather than indirectly via a reduction in interference. It is suggested that a particular phase of the rising blood alcohol curve (0.02–0.03 g/100 ml) facilitates trace consolidation. The facilitating and possibly excitatory effects of alcohol may be important for understanding the rewarding aspects of drinking.

A probable neuroleptic effect on platelet monoamine oxidase in chronic schizophrenic patients

Platelet monoamine oxidase activity (MAO) was studied serially over time in 16 chronic schizophrenic patients when medication free and then when medicated. Thirteen of the 16 patients had significant decreases in platelet MAO activity following neuroleptic drug treatment. The change in MAO activity was found to be correlated with response to treatment and to dose of medication.

Topographic Differences between Normals and Schizophrenics: The N120 Evoked Potential Component

Topographic differences in evoked potentials were measured in 20 off-medication chronic schizophrenics and 24 normal controls. Four intensities of brief electrical shocks were administered to the subjects right forearm in a random order at 1-second intervals. Evoked potentials (EPs) were recorded from the scalp over the left hemisphere. The EP data from 16 left hemisphere leads were used to generate EP maps of brain response for individual subjects. The maps were normalized by z transformation. Group mean maps of EP activity and unpaired t tests were then computed. Normals showed strongly localized activity in the pre- and postcentral gyri, with increasing intensity resulting in the attenuation of parietal response. Schizophrenics showed more diffuse EP activity which did not vary with intensity. Significant differences between normals and schizophrenics were found for all four intensities in posterior frontal and anterior parietal cortex. This is consistent with the findings of small EPs reported by others in the somatosensory, visual and auditory modalities.

The Genain quadruplets: Electrophysiological, positron emission, and x-ray tomographic studies

Four 51-year-old monozygotic quadruplets concordant for schizophrenia, originally studied at the National Institute of Mental Health 25 years ago, were restudied with topographic electroencephalography (EEG), evoked potentials (EPs), computed tomography (CT scans), polysomnographic sleep recordings, and positron emission tomography (PET) with 18F-2-deoxyglucose. EEG and EP findings were consistent with those from other groups of patients with schizophrenia and showed great similarity within the quadruplets. CT scans revealed uniformly small lateral ventricles. PET scans replicated earlier findings of relatively low glucose use in the frontal lobes but did not show strong familial concordance.

TOPOGRAPHIC ANALYSIS OF COMPUTER PROCESSED ELECTROENCEPHALOGRAPHY IN SCHIZOPHRENIA

Electroencephalography has been employed as a tool in the investigation of schizophrenia for many years. Nevertheless, one of the major problems limiting the utility of EEG in psychiatric research has been the difficulty in quantifying, localizing and analyzing the massive amounts of data generated by multiple electrode recordings. The development of the topographic technique of brain electrical activity mapping (BEAM) provides a method of condensation of spatiotemporal information that may be easily grasped by visual inspection and is intuitively meaningful. A case of a chronic schizophrenic patient is given as an example to demonstrate this procedure and a statistical method of analysis employing significance probability maps (SPM) is shown. The method provides a technique of EEG analysis that is highly compatible with other existing color map topographies such as CT scan, PET scan and cerebral blood flow and involving less risk.