Opto-fMRI
fMRI has traditionally been used for mapping the brain and correlating brain function with specific structures. The method has become a sort of laughing-stock within the electrophysiological community because of the countless studies that proclaim region A to be responsible for function B. A typical blunder can go like this: "Increased activation of the amygdala during a fear conditioning task suggests that the amygdala is the brain's fear center." To be fair, the method is still very useful and serious scientists don't fall into this fallacy as much as the popular media does. Some outstanding questions are what the measured signal (blood oxygenation level; BOLD) actually means for neural activity; whether it's possible to disambiguate excitation from inhibition; how activation in one region affects connected regions; and what the causal relationships among activated regions are. To address the last two of these, Ed Boyden and colleagues at MIT used a combination of optogenetics and fMRI (Opto-fMRI) in awake mice. The idea is that if they can change the dynamics of a defined population of cells in a localized and fast way (they infected pyramidal cells in mouse somatosensory cortex with ChR2), the network effects of that activation would be revealed by fMRI. In this way, they validate the network effects in both technologies. One limitation that's still inherent to fMRI is the slow temporal resolution - while optogenetic stimulation changes membrane potential with millisecond-resolution, fMRI's hemodynamic response is much slower. Perhaps other imaging methods like multiphoton imaging may be used in the future to dissect large-scale circuits in awake animals.