CORTICAL-STRIATAL-THALAMIC CIRCUITS AND BRAIN GLUCOSE METABOLIC-ACTIVITY IN 70 UNMEDICATED MALE-SCHIZOPHRENIC PATIENTS

Objective: The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in sc hizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its mai n symptoms. Method: Seventy male schizophrenic patients underwent [F-1 8]-fluorodeoxyglucose positron emission tomography after a period of a t least 4 weeks during which they had not received neuroleptic medicat ion and were compared to 30 age-matched male normal comparison subject s. Results: Analyses revealed decreased metabolism in medial frontal c ortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ven tral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previ ous studies, the schizophrenic group had lower hypofrontality scores ( ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic pa tients did not differ from that of comparison subjects, while occipita l cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal acti vity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for ea ch schizophrenic patient on the scan day, were correlated with regiona l brain glucose metabolic rate. Medial frontal cortical and thalamic a ctivity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and h ypofrontality scores did not significantly correlate with negative sym ptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. Conclusions: Low metabolic rat es were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striata l-thalamic pathways in schizophrenia. Loss of normal lateralization pa tterns was also observed on an exploratory basis. Correlations with ne gative symptoms and group differences were more prominent in medial th an lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.