This proposal documents our development of the neuromagnetic current probe from a crude and highly theoretical investigational device to a group of productive research instruments on the brink of clinical application. We propose a course of research that will enable us to continue to refine these techniques while applying them to test fundamental hypotheses in basic and clinical neuroscience. Since our first recordings of the magnetic field of an isolated nerve bundle in 1979, we have demonstrated the advantages offered by direct magnetic measurements of cellular action currents in vertebrate and invertebrate nerves. We have also developed mathematical models for analyzing the unique data obtained in these studies. In the course of developing models and improving the instruments for magnetic recording, we have identified specific applications for magnetic, techniques to address problems having significance for basic biomedical research and clinical medicine. Our past studies have provided us with a detailed understanding of the relationship between the electric and magnetic action signals of nerves. The unique properties of magnetic recording systems make them particularly practical for examining peripheral nerve injury, repair and regeneration in animal models and humans. We have developed a magnetic device that can be safely and effectively used in an operating room, and have developed a SQUID magnetometer having unprecedented resolution for use in our studies. Clinically-relevant studies include elucidating mechanisms of surgical tourniquet-induced nerve injury to determine means of prevention; assessing the effect of nerve compression in carpal tunnel syndrome, and aiding surgeons' selection of strategies to optimize repair of neuroma-in-continuity. Basic studies include characterization of action currents in single axons and peripheral nerve bundles in normal and injured states. We will exploit the magnetic current probes' non-traumatic scanning capability to examine axonal transport, impulse initiation, and the virtual cathode effect in squid giant axons, and to study neurotransmission at squid giant synapses. An implantable toroidal magnetic probe may afford longterm study of nerve regeneration. Completion of the proposed studies should provide new, basic information in neurophysiology, establish magnetic recording as a productive instrument for biomedical research and clinical application, and enhance the quality and safety of patient care.
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