The long-term objective of this Program Project is to create a foundation for the application of functional magnetic resonance imaging (FMRI) to medicine. It is proposed to define the physiological basis of the FMRI response (Project I) and to use FMRI to investigate the cerebral organization of vision (Project II), motor control (Project III), and audition and language (Project IV). Project I will distinguish and quantify contributions of task-induced changes in blood oxygenation and capillary flow to FMRI contrast, using the technology of FMRI physics as well as invasive physiological studies in rats. Project I specifically proposes strategies to distinguish parenchymal FMRI response from FMRI signals arising from changes in flow and oxygenation in collecting veins. The three neuroscience projects (II-IV) each begin by examining the parametric relationships between stimulus and movement variables and FMRI signal change. Project II will compare functional maps of the human and simian visual association cortex. Projects II and III will evaluate parallel hypotheses regarding the retinotopic and somatotopic organization of the visual and motor systems. In later years, all three projects will use complex task activation experiments to assess FMR signal changes in polymodal cortex. Projects II and IV will collaborate in investigating polymodal spatial localization and semantic processing. Projects III and IV will collaborate in defining the brain regions involved in timing operations associated with auditory processing and movement. Project IV will determine the organization of auditory cortical regions specialized for speech perception. These projects will be supported by Core A- Administration and Scanner Operation, Core B-Image Acquisition and Processing, which proposes fundamental advances in FMRI technology and signal processing in addition to providing computer services, and Core C- Subject Interface Systems, which is concerned with delivery of stimuli and monitoring of physiological and movement variables. There are four significant technological aspects of the proposal. 1) Purchase of a powerful computer is proposed that will permit real-time display of FMRI signals. 2) Use of a unique head gradient coil with several significant benefits for FMRI. 3) Application of advanced mathematics and statistical procedures for signal analysis, and 4) comparison of FMRI signals obtained at 0.5, 1.5, and 3 T, giving a unique capability to investigate the field- strength dependence of response. FMRI will have a major impact on the clinical disciplines of psychiatry, neurology, neurosurgery, and neuroradiology, leading to improved patient diagnosis, treatment planning, response to treatment, and monitoring of disease. A multidisciplinary effort linking biophysics, physiology, and neuroscience is proposed in order that the technical, methodological, and neuroscientific principles of FMRI can be comprehensively defined as a basis for clinical applications.
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