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Volume 16, Number 21, Issue of November 1, 1996 pp. 7055-7062
Copyright ©1996 Society for Neuroscience

Local and Distributed Effects of Apomorphine on Fronto-Temporal Function in Acute Unmedicated Schizophrenia

Received May 23, 1996; revised Aug. 7, 1996; accepted Aug. 9, 1996.

Paul C. Fletcher^{1, 3}, Christopher D. Frith¹, Paul M. Grasby², Karl J. Friston¹, and Raymond J. Dolan^{1, 3}

¹ Wellcome Department of Cognitive Neurology, Institute of Neurology, London WC1N 3BG, United Kingdom, ² MRC Cyclotron Unit, Hammersmith Hospital, London W12, United Kingdom, and ³ Royal Free Hospital School of Medicine, London NW3, United Kingdom

We used positron emission tomography (PET) to measure brain activity in healthy control subjects and unmedicated patients with schizophrenia. Subjects were scanned in the context of a combined psychological and pharmacological challenge, and we examined the effects of apomorphine, a drug acting on dopamine receptors, on brain systems engaged by a paced verbal fluency task. This factorial design enabled comparison of control subjects and schizophrenics in terms of the activations engendered by the cognitive task and the pharmacological challenge and the interaction of the two. We report a failure of cognitive task-related activation in anterior cingulate cortex and of task-related deactivation in the left superior temporal gyrus in the schizophrenic subjects. Compared with controls, the impaired cingulate activation was significantly reversed by apomorphine. Additionally, there was a trend for the abnormal fronto-temporal pattern of activation in schizophrenic subjects to be normalized by the drug. Overall, in schizophrenic subjects the effect of apomorphine, which we interpret in terms of a net dopaminergic antagonism, was to modify the brain activity, making the pattern more akin to that seen in control subjects. The results indicate both a regionally specific abnormality of brain function in schizophrenia and an abnormal pattern of fronto-temporal interactions.

Key words: PET; schizophrenia; apomorphine; verbal fluency; fronto-temporal interaction

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