The broad objective of the proposed research is to advance currently available neuro-imaging techniques in order to facilitate their application to disorders characterized by cognitive and behavioral dysfunction. The specific aims of this proposal are to improve image analysis methods for integrating anatomical MR images and functional PET images of regional cerebral blood flow obtained by using H215O and apply behavioral/physiological techniques to generate cognitive signals that are valuable in understanding localized dysfunction in demented patients. There are three major components in the development of image analysis methods: (1) Image registration: Improved methods based on surface- fitting techniques will be developed for spatially registering a set of MR images with a series of PET emission images that are acquired by injecting H215O to the same subject under different behavioral/physiological conditions; (2) Image interpolation: Accurate interpolation schemes for both the shapes of the brain surface and the intensity levels of brain images will be developed using an dynamic elastic force field model to generate more complete 3-D brain image data sets; and (3) Image subtraction: New techniques will be developed for detecting, localizing, and enhancing the cognitive signals by subtracting PET images at a baseline state from images at a stimulus state. The detected cognitive signals will be also be in registration with the anatomical map provided by MR images. In developing behavioral/physiological techniques, three procedures will be used to generate cognitively induced signals for understanding localized dysfunction in demented patients: (1) Modified Sternberg procedure, in which signals related to short-term memory will be assessed; (2) Serial reaction time procedure, in which signals related to implicit memory will be evaluated; and (3) Verbal comprehension procedure, which will be employed to enhance global cerebral flow. The results of this research will be of value in determining the neuronal systems affected in the dementia of Alzheimer's disease and related degenerative disorders and contribute to an improved understanding of the pathophysiological mechanisms involved in the degenerative processes.