Functional MRI is a noninvasive neuroimaging method that indirectly measures neuronal electrical activity by tracing localized changes in blood flow, blood volume and oxygenation levels associated with increased brain activity. Although these changes have been shown to be roughly proportional to underlying neuronal activity, they occur on a slower timescale and on a somewhat more coarse spatial scale. There also are many variables not related to neuronal activity that can influence changes in blood flow, making interpretation of the magnetic resonance signal challenging. Therefore, more direct measures of neuronal activity are desired. Scientists at the National Institute of Mental Health in Bethesda, Md., have demonstrated that magnetic resonance can detect magnetic field changes that are not related to changes in blood flow but that are induced by cortical electrical activity. Their findings suggest the feasibility of using functional MRI as a direct and reliable method of mapping brain activity. To eliminate the confounding effect of blood flow, the researchers scanned rat-brain tissue cultures that were devoid of blood vessels yet spontaneously active and that emitted bursts of neuronal activity at about 10 Hz. Magnetic resonance data was acquired during these bursts and after neuronal activity was chemically blocked with a neurotoxin. The cultures were grown on multielectrode arrays to enable recording of local field potentials before and after the MR sessions, which provided a direct, independent measure of neuronal electrical activity for comparison with the magnetic resonance data. The scientists obtained magnetic resonance measurements using a 7-T MRI scanner from Bruker Biosciences Corp. of Billerica, Mass., and a free induction decay technique that enables high temporal resolution and sensitivity. Free induction decay is a magnetic resonance signal that is generated as nuclei, excited by an external magnetic field, relax back to the equilibrium state. In this case, the decay signal lasted less than 100 ms. Local field potential recordings and magnetic resonance measurements taken of rat-brain cultures attached to multielectrode arrays (shown above) indicate the feasibility of an alternative MRI technique for directly detecting neuronal electrical activity. Because the magnetic resonance scanner typically is used for larger samples, the researchers created a cradle to hold the multielectrode arrays and a radio frequency transmit/receive surface coil. The cradle and the coil were made smaller so that the sensitive area of the coil matched the size of the sample, maximizing the signal-to-noise ratio and improving the instrument’s sensitivity. The magnetic resonance measurements were highly correlated with the local field potential recordings of the same cultures before and after neuronal activity was blocked. Both the magnetic resonance and the local field potential signals stopped when activity was blocked, indicating that the changes in magnetic resonance signals most likely were a result of electrical discharges from neurons. According to Peter A. Bandettini, director of the institute’s functional MRI facility, if this technique were to become feasible for detecting signal changes in the human brain during neuronal activity, the information obtainable by MRI about brain function would be more detailed and interpretable than that obtained using measurements of blood flow and oxygenation levels, making functional MRI more clinically applicable. However, signal changes in the human brain that might be detected with this technique are expected to be about an order of magnitude smaller than those typically detected using functional MRI based on blood oxygenation level dependent contrast. The investigators are pursuing several avenues of research focused on increasing the temporal and spatial resolution, interpretability, and clinical applications of functional MRI. PNAS, Oct. 24, 2006, pp. 16015-16020