Positron emission tomography (PET) provides non-invasive, quantitative, in vivo, measurements of regional cerebral blood flow (rCBF) and regional cerebral metabolic rate (rCMR) in man. Regional CBF and CMR vary directly with the regional rate of cerebral neuronal activity in the brain. Oxygen 15-H2O PET is a new PET methodology employing oxygen 15 in water (oxygen 15 half life = 123 sec) as a diffusible blood flow tracer to measure rCBF. Oxygen 15-H2O PET is uniquely suited to the study of focal cerebral function because of the brief (40 sec) scan duration, good resolution and the capacity for rapidly sequential scans (8 rCBF scans in 90 min) in a single individual. We propose to use oxygen 15-H2O PET to measure rCBF in normal volunteers during maneuvers designed to induce focal activations of discrete, cortical neuron populations. Initial studies will delineate response characteristics of somatic sensory neurons to electrocutaneous stimuli ranging in frequency from slow (2-10 Hz) to flutter (40-80 Hz) to vibration (100-500 Hz). Stimulus frequencies are chosen on the basis of the known response characteristics of cortical somatic sensory neurons in primates. When stimuli inducing consistent cortical rCBF responses are defined, they will be employed for more complex stimulus paradigms. Complex paradigms will be intended to induce focal cortical changes via cognitive tasks including pattern recognition, directed attention and language, all using somatic sensory stimuli as the vehicle. In this way the activation induced by the simple stimuli themselves will be well known, allowing discrimination of the regional changes due to the higher-order cognitive activity from rCBF change due to the stimulus alone. These experiments will provide a foundation for continued work on human cortical neurophysiology with the long-range intent of exploring progressively more complex human behaviors. Precise quantitation of the cortical CBF changes induced by simple, reproducible stimuli will also be the basis for studies of neurological pathophysiology, as these stimuli may then be used to generate cortical activation in individuals with neurological disease.
