The purpose of the study is to investigate SPECT blood flow measurement of cortical activation when the ligand is administered as a steady infusion over a 5-6 minute period of time, rather than a bolus dose at one time. In addition, the Wisconsin Card Sorting Test, used as the activating task, was first taught to subjects so that the activation effect could be ascribed as due to the cognitive actions of performing the test rather than learning the test. The methodology for the performance of the Wisconsin Card Sorting Test (WCST) was developed for computer administration, providing the most reliable means of task performance for the subjects. Subjects were taught the WCST task prior to SPECT imaging. The logic for this was to remove sources of variance in WCST performance due to learning effects, rather than continuous performance of the cognitive functions needed to perform the WCST. WCST performance was recorded, and all subjects performed very well on it. Details of administration of the SPECT ligand using a perfusion pump were established. This entailed determination of fluid volumes within the IV tubing, and calculation of flow rates. A perfusion rate was used to provide 5-6 minutes of constant administration of SPECT ligand to the subject. The perfusion was begun shortly after subjects began the task (either control task or WCST activation task), and ended before subjects completed the task. Five normal subjects have been assessed with two SPECT scans each, the baseline control task and the activation task. All subjects performed well on the WCST activation task. SPECT image data has been analyzed. Statistical Parametric Mapping (SPM) has been used to normalize images with respect to standard neuroanatomical references points. This involves identification of landmarks, and rotation and translation of the image data sets. After normalization, the baseline control task images have been digitally subtracted from the WCST activation task. These differences have been pooled across all five subjects. Activation was larger in the right frontal lobe, and inferior parietal, superior temporal, and orbito-medial frontal areas showed significant activation. Inactivation was greatest on the right side in the area of the hippocampus, and somewhat less pronounced in the left hippocampus. These findings are similar to results published by other groups for WCST activation, but differ in showing involvement of orbito-medial frontal areas.

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