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GRAY MATTER HETEROTOPIAS IN SCHIZOPHRENIA

P.C. Nopoulos*, M.A. Flaum, N.C. Andreasen,

V.W. Swayze

University of towa Hospitals and Clinics, Mental Health Clinical Research Center, 200 Hawkins Drive, Iowa City, IA 52242-1057, USA

Gray matter heterotopia (GMH) is a type of neuronal migra-

tion anomaly in which ectopic cortex is present within the depth

of the cerebral white matter. Prior to the advent of modem

imaging techniques, GMH had been considered to be rare and usu-

ally associated with severe congenital malformations, and to be

manifested clinically by seizures and profound cognitive, motor

and language deficits.

Magnetic resonance imaging allows for the in vivo detection

of GMH. We have observed two such cases in patients present-

ing with symptoms of schizophrenia, but no neurological abnor-

malities, and otherwise normal MRI’s. In one case, the GMH

was relatively small (about 1 cm’) and located in the left frontal

lobe, near the genu of the corpus collosum. The other lesion was

larger and more irregular, and bordered on the right posterior as-

pect of the hippocampus.

While the incidence of GMH among normals is unknown at

this time, we postulate that this particular anomaly may occur in

schizophrenics at a higher rate than in the normal population.

Furthermore, neuronal migration abnormalities may be involved

in the pathogenesis for a small subset of schizophrenics.

A PET STUDY OF DIFFERENTIAL PATl-‘ERNS OF BRAIN ACTIVATION IN SPEM VS. SACCADIC EYE MOVEMENTS

Gillian O’Driscoll*, Steven Strakowski, Nathaniel Alpert, Philip S. Holzman

Psychology Dept., Harvard University, William James Hall, 33 Kirkland St., Cambridge, MA 02138, USA

Reports indicate that schizophrenic patients and their unaffected

relatives have intact saccadic eye movements but impaired smooth

pursuit eye movements (SPEM). This pattern has not been found

in psychiatric controls, suggesting that SPEM dysfunction may be

a marker for schizophrenia. To determine the brain areas that

mediate this apparent genetic deficit, we used PET to study

normals (N=13) performing these two tasks. We hypothesized that

SPEM makes a greater demand on frontal structures than do sac-

cadic eye movements since frontal eye field activation is neces-

sary to inhibit superior colliculus generation of saccades.

Five areas showed differentially greater activation during

SPEM: the frontal eye fields, the middle frontal cortex, the ante-

rior cingulate, the inferior parietal lobe, and the occipital lobules.

The anterior cingulate has been proposed to lie at the centre of a

network of five structures implicated in schizophrenic pathology

(Benes, in press). It is hypothesized that tasks using any of these

structures will require integration via the anterior cingulate, and

that the pathological process in schizophrenia may lie in the an-

terior cingulate or in one of the other network structures. Four

of the five structures were found to be important to SPEM, pro-

viding tentative support for their operation as a network. A fu-

ture study will look at these regions during impaired SPEM vs.

saccadic eve movements in relatives of schizophrenics.

IMPAIRED INTERHEMISPHERIC INTEGRATION IN BRAIN OXYGENATION AND HEMODYNAMICS IN SCHIZOPHRENIA

F. Okada*, Y. Tokumitsu**, Y. Hoshi***, M. Tamura***

*Health Administration Center, **Department of Pharmacology, ***Institute for Electronic Science, Hokkaido University, Sapporo, Japan 060

Some of the symptomatology of schizophrenia have been pre-

sumed to occur as a result of defects in functional connections

between different regions of the brain. Since the report of struc-

tural callosal pathology in schizophrenia, many reports of defec-

tive callosal transfer in schizophrenia have cited visual, auditory

and tactile stimuli, as well as somatosensory evoked potentials

over the past ten years. To measure disturbances of interhemi-

spheric integration in brain metabolism and hemodynamics dur-

ing a psychological task, we examined 38 patients with chronic

schizophrenia who met DSM-III-R criteria. A same number of

age and sex matched healthy volunteers served as controls. Si-

multaneous monitoring by near-infrared (NIR) spectrophotometry

of hemoglobin (Hb) in both hemispheres of the forebrain during

mirror drawing task (MDT) was performed. In response to the

MDT, normal volunteers showed uniform patterns of changes in

oxygenation; bilaterally simultaneous increases of oxygenated Hb

and decreases of deoxygenated Hb and gender- and handedness-

related differences of hemodynamics between the hemispheres of

the brain. On the other hand, half the schizophrenics showed

dysregulated patterns between hemispheres which never appeared

in normal volunteers. Schizophrenics showed none of the

lateralization which was commonly observed in normal male vol-

unteers. Certain schizophrenic symptoms might be related to de-

fective interhemispheric integration.

PET STUDIES OF REGIONAL CEREBRAL BLOOD FLOW (rCBF) IN SCHIZOPHRENICS AND CONTROLS: EFFECTS OF LEVELS OF LANGUAGE AND ATTENTION

D.S. O’Leary*, R.R Hurtig, R.D. Hichwa, G.L. Watkins, L.L. Boles-Ponto, M.L. Kesler, M. Rogers, P.T. Kirschner, N.C. Andreasen

UIHC, 2911 JPP, 200 Hawkins Drive, Iowa City, IA 52242- 1057, USA