The year long goal of this project is to determine the extent to which functional magnetic resonance imaging (fMRI) can be used to more precisely localize cortical activation in the service of the Wisconsin Card Task (WCST) a """"""""gold standard"""""""" in assessing prefrontal cortex (PFC) function. The putative constituent cognitive operations of the WCST including concept formation, use of feedback (thought to employ working memory), and set shifting will also be assessed. The proposed studies combine a new neuroimaging method with high spatial and temporal resolution, with novel experimental designs to more specifically parse the cognitive operations thought to subserve the WCST, compared with previous nuclear medicine based studies involving clinical neuropsychological tests. These studies will provide localizing information about the WCST both by convexity (dorsolateral, orbitofrontal, mesial) and by side. They will also help to generate, more specific cognitive tasks to study the functional neuroanatomy of prefrontal cortex. The increased precision in our understanding of normal human PFC function should allow for better comparison to primate and human neuropathological models of prefrontal function. In this proposal, fMRI will be used to study normal subjects. This will be used as baseline data for later efforts to study the pathophysiology and therapy of schizophrenia.
SPECIFIC AIMS 1. To localize cerebral activation by side, and within the three primary convexities of the frontal cortex (dorsolateral, orbitofrontal, mesial) during the WCST. 2. To determine the extent to which concept formation accounts for PFC activation in the WCSR. 3. To determine the extent to which working memory accounts for PFC activation in the WCST. 4. To determine the extent to which set shifting accounts for PFC activation in the WCST. RESEARCH DESIGN AND METHODS Cognitive challenge will be achieved with three primary tasks, the WCST, and an object and visual spatial working memory task. These tasks are designed in an off-on-off sequence which has proven effective in identifying which voxels of brain tissues have activation comparable to the cognitive activation input function. Variations in the WCST will provide data to study the effects of concept formation and set shifting. Data from two novel working memory tasks will also be compared to the WCST data. Cerebral activity will be assessed with the blood oxygen level dependent (BOLDS), fMRI method. Alterations in blood oxy and deoxyhemoglobin levels provide an index of cerebral blood flow, a measure of neural activity.
