This proposal is aimed for development and optimization of a novel neuroimaging method, termed "magnetic source MRI" (msMRI), that uses a conventional MRI scanner in an innovative manner to measure electromagnetic signals from populations of neurons. The msMRI technique is based on directly detecting MRI signal changes associated with changes in magnetic fields concomitant with neuronal filing. Compared with positron-emission tomography (PET) and functional MRI (FMRI) methods, msMRI has improved spatial localization and significantly better temporal resolution. Compared with magnetoencephalography (MEG) and electrophysiology (EEG), msMRI has superior spatial resolution. The goal of this project is to systemically characterize rnsMRI signal, apply this unique technique in initial human neuroscience research, and facilitate the use of msMRI among scientists investigating basic neurophysiological and neuropsychological phenomena as well as accurate clinical diagnostic/intervention methodology for brain diseases. Three specific aims are proposed for three years: (1) to refine and extend mathematical models of msMRI; (2) to optimize strategies for data acquisition and analysis; (3) to evaluate the extent to which msMRI signal fulfills the requirements of linear systems and its dependence on magnetic field strength. This proposal is a perfect match of the mission of the NIBIB because the proposed msMRI is an innovative imaging technology that should significantly impact on research and clinical developments in the fields of human neuroimaging, cognitive neuroscience, and neuropathology. Magnetic source MRI could represent a substantial advance for these fields and should help bridge the gap between human neuroimaging and electrophysiological methods employed in experiments with non-humans. The power provided by msMRI technology is essential to understand human cellular neurophysiology and its implication on brain diseases.