Much of our knowledge of
brain function has been gleaned from studies using
microelectrodes to characterize the response properties of individual
neurons in vivo. However, because it is difficult to accurately determine the location of a
microelectrode tip within
the brain, it is impossible to systematically map the fine three-dimensional spatial organization of many
brain areas, especially in deep structures. Here, we present a practical method based on digital stereo microfocal x-ray imaging that makes it possible to estimate the 3D position of each and every
microelectrode recording site in "real time" during experimental sessions. We determined the system's
ex vivo localization
accuracy to be better than 50 microm, and we show how we have used this method to co-register hundreds of deep-brain
microelectrode recordings in monkeys to a common frame of reference with
median error of less than 150 microm. We further show how we can co-register those sites with magnetic
resonance (MR) images, allowing for comparison with
anatomy, and laying the groundwork for more detailed
electrophysiology/
fMRI comparison. Minimally, this method allows one to marry the single-cell specificity of
microelectrode recording with the spatial mapping abilities of imaging techniques, and it has the potential of yielding fundamentally new kinds of high-resolution maps of
brain function.
