At the NIH, the Neurophysiology Imaging Facility is a core facility dedicated to the MRI scanning of nonhuman primates. The NIF, which was founded in 2004, offers services to a wide range of investigators in each of the three sponsoring institutes (NIMH, NINDS, and NEI). These services assist in the research effort of many investigators in the thriving NIH nonhuman primate community. Anatomical scans allow for the identification and verification of brain structures in vivo. Scientists needing to localize a neural circuit of interest or investigating the distribution of a new drug in the brain are able to quickly and easily scan their animals in the facility. Functional scans (fMRI), conducted in animals performing a host of behavioral tasks, allow for the assessment of brain activity, thus providing a bridge to the wealth of human fMRI studies. Both structural and functional imaging in the NIF exploit the latest cutting-edge MRI imaging technology, allowing users to combine imaging with other invasive techniques, such as microelectrode recordings, pharmacological inactivation, or anatomical tract tracing. The facility develops, designs, builds, and maintains radio frequency (RF) coils for a range of imaging needs. Testing animals inside a strong magnetic field has required the development of a wide array of MRI-compatible equipment, including animal chairs, restraint devices, reward delivery apparatus, eye position tracking cameras, and manual response keys. Users are set up with RF coils and these other devices, allowing them to initiate their studies with minimal development on their part. Structural scans: Using the standard setup, the facility staff assists with scans that aid in MRI-targeting of electrophysiological sites, identification of microelectrode positions, evaluation of experimental precision, and, importantly, the direct comparison of electrical recording sites with foci of fMRI responses in the context of a cognitive task. We are further able to combine these techniques with (1) reversible inactivation of electrical neural activity using pharmacological agents, (2) the identification of anatomical pathways using transported, MRI-visible chemicals such as manganese chloride, and (3) electrical microstimulation, where small local currents activate neurons that project to regions that can be detected using the fMRI signal. Surgical targeting is another relies upon particularly high-quality, distortion-free 3-D images of the brain. We have recently implemented algorithms that measure and compensate for small geometric distortions in the images that might hamper surgical precision. The facility also offers a frameless stereotaxy protocol to assist the surgeon with implantation. This method permits a visualization of the high-resolution scan during surgery, with a real-time depiction of the surgical instruments relative to the scanned brain structures. We have used this approach routinely to aid in the accurate implantation of electrode bundles and chronic cannulae, targeted ablations, and the placement of recording chambers. Functional MRI scans: The most unique aspect of the facility is the capacity to conduct fMRI simultaneous with other measurements and perturbations. The Intramural Research Program at the NIH is one of the very few sites around the world in which monkeys can routinely participate in both fMRI and electrophysiological studies. The fMRI studies go beyond mapping functional specialization in the brain. Experiments within the facility typically combine fMRI with other, invasive procedures, such as microelectrode recordings or pharmacological inactivation. In the last year, neuroscience have combined fMRI with cortical ablation, pharmacological inactivation, electrocorticogram recordings, electrical microstimulation, and recordings from chronic microwire arrays. The fMRI experiments produce large data files that must be processed to evaluate the functional activity patterns across the brain. The facility provides storage of these data, as well as help in the initial processing steps. Ex-vivo MRI scans for diffusion MRI: The core facility also carries out some diffusion weighted (DTI) scanning of, both in vivo and ex vivo. Recently, Dr. Ye in the facility has led an investigation exploring the possibilities of DTI, and the associated tractography methods. To do this, multiple macaque and marmoset brains were scanned ex vivo, each for up to 72 hours continuously. This approach allowed for sufficient signal to noise and angular resolution that might foreshadow in vivo human data acquisition in the future. These very high quality brain samples were analyzed in multiple ways, with one publication nearing publication Thomas et al, (2014), and a second one nearing submission. These studies aim to clarify the promise and inherent limits of diffusion tractography in the human brain , now and in the near future.
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