Existing functional brain MR imaging methods such as blood oxygenation level dependent (BOLD) imaging are based on vascular and metabolic responses to variations in underlying neuronal activity and thus reflect the latter only indirectly. It has been proposed (e.g. Bodurka & Bandettini, 2002) that magnetic field perturbations caused by neuronal currents in the brain in principle ought to be detectable by means of MRI. Several research groups have demonstrated the feasibility of this idea in theory, electric current phantoms and in vivo. However, relatively low signal-to-noise ratio achieved to date renders existing methods impractical. Balanced Steady State Free Precession (bSSFP, also known as TrueFISP, FIESTA) pulse sequence is unique in that it can afford the highest known SNR per unit time and thus application of bSSFP for functional neural current imaging can potentially solve the problem of low SNR. Recent studies suggest that certain SSFP sequences might be exquisitely sensitive to minute periodic perturbations of the spin phase. Thus, periodic currents locked to RF excitation pulse result in an alternating balanced steady state (ABSS) that can effectively amplify the phase offset induced by currents. Our theoretical calculations and the data acquired with bSSFP at 3T using a current phantom indicates SNR of the signal induced by periodic currents that is substantially superior to that achieved previously using standard gradient and spin echo imaging (Buracas et al., 2007). We propose to develop optimized alternating steady-state imaging protocols for imaging of periodic electric currents. First, we will optimize, analytically, in computer simulations, and current phantom experiments the sensitivity of the ABSS method to weak periodic currents and address the impact of various sources of noise on the ABSS signal. Next, we will apply this method to imaging neuronal currents in vivo (using rat whisker stimulation and human audiovisual stimulation paradigms). We will implement noise compensation for magnetic field fluctuation due to respiration and scanner drift and motion compensation. In conclusion, the current proposal will address the possibility to measure electromagnetic correlates of cerebral neuronal activity by means of ABSS and will address critical sources of noise. Accomplishment of the proposed aims has a potential of introducing a new imaging modality for functional brain imaging - high resolution MRI-based magnetoencephalography. PUBLIC HEALTH RELEVANCE: Established functional brain MR imaging methods are susceptible to factors influencing neurovascular coupling. It has been recently proposed and demonstrated that MRI can be used for imaging neuronal currents directly, but existing methods are impractical due to their low SNR. The proposed research will develop ultra- sensitive MRI methods for imaging neuronal currents using balanced Steady State Free Precession pulse sequences that possess best known SNR efficiency. [unreadable] [unreadable] [unreadable]