This study will explore the possibility of using a molecular imaging technique to detect neurotransmitters released during performance of a cognitive task. The technique is currently used to examine chronic changes in binding potentials because the conventional methods are not suitable for detection of acute changes. We have recently demonstrated that the method can be modified to allow detection of acute changes. Using this modified method, we detected the release of striatal dopamine during performance of a motor planning task. The technique however requires further validation and testing before it can be reliably used to study human cognition. First two experiments will examine whether the modified technique generates false positive or false negative results. False positive effect will be tested using a control (no-activation) experiment which will not release dopamine. This experiment will also help us determine the range of 'normal' variation in the rate of ligand displacement. False negative results will be tested using an amphetamine challenge test. Because amphetamine is known to enhance striatal dopaminergic activity, the rate of ligand displacement should increase after the drug administration. The study will also evaluate whether the technique can be used to advance our understanding of human cognition. The evaluation will include examination of its ability to acquire information about the neurotransmission associated with a cognitive task. We propose to study a dopamine dependent task (implicit motor memory) to ensure that the modified technique is sensitive to isolate and detect striatal dopamine released during cognitive processing. The evaluation will also include examination of the ability of the technique to probe cognitive controversies. We propose to probe the controversy concerning striatal processing of nonprocedural memory tasks that are impaired following striatal lesions. Because these tasks do not consistently activate basal ganglia in neuroimaging studies, striatal involvement in the processing is unclear. Detection of striatal dopamine release in this experiment will support the findings of lesion studies and may indicate that, the striatal processing elicits sub-threshold hemodynamic response. A negative result will suggest nondopaminergic or extrastriatal processing of these tasks. This study will determine whether the molecular imaging technique can be reliably used to investigate an unexplored aspect (neurotransmission) of human cognition. ? ?
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