The major areas of effort in this project have been (1) to develop new tracers or other approaches for the study of neurotransmitter function in normal and abnormal physiology; and (2) to apply what tracer methodologies we have available to the study of neuropsychiatric disorders. To these ends, the following achievements are notable. A series of studies of (18F)-cyclofoxy have been completed in baboons that delineate its usefulness as a measure of opiate receptor avidity. An application for its use in humans has been submitted to the Food and Drug Administration. We found that we could successfully apply PET measurement of glucose metabolism to determine biological determinants of attention as we observed for what we believe to be the first time a direct relationship between the metabolic activity of a brain region, the mid-prefrontal cortex and quantitative measures of the accuracy of ongoing performance of auditory discrimination in normals. In patients with in the middle prefrontal cortex was found to be significantly lower than normal and unrelated to performance. Furthermore, preliminary analysis suggests that medicated patients with schizophrenia demonstrate a similar relationship between the middle prefrontal cortex and performance as normal controls. The findings point to a role of the mid-prefrontal cortex and its dopamine neurotransmitter pathway input in sustained attention and to dysfunction of this region and of its dopamine modulation in some patients with schizophrenia.
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