The physics behind magnetic resonance imaging, or MRI, is quite complicated and based on nuclear spin properties of protons comprising different brain tissues. Through a remarkable set of engineering achievements, it is now routine to visualize the entire body, including the brain, in three dimensions. Perhaps even more impressively, the flow of blood, its relative proportion in the tissue, and its oxygenation level, can all be monitored using standard methods. The latter functional MRI (fMRI) is now used by investigators in nearly every major university in the country and around the world to explore sensory processing, executive function, and social cognition. In just two decades, the fMRI revolution has brought the study of the human brain to the forefront of neuroscience, and has shaped the societal understanding of what brain activity is. At the NIH, the Neurophysiology Imaging Facility is a dedicated core for the MRI scanning of nonhuman primates. The NIF is a centralized core facility that offers services to a wide range of investigators in each of the three sponsoring institutes (NIMH, NINDS, and NEI). The service that NIF provides 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) in animals performing a host of behavioral tasks allows 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 imaging technology, allowing users to combine imaging with other invasive techniques, such as microelectrode recordings, pharmacological inactivation, or anatomical tract tracing. 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 these devices, allowing them to initiate their studies with minimal development on their part. STRUCTURAL SCANS: Using the standard setup, we are able to do routine MRI-targeting of electrophysiological sites, microelectrode recordings, evaluation of experimental precision, and, importantly, the direct comparison of electrical with 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 main objective for high-resolution scanning in the NIF core facility. This relies upon 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 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. EX-VIVO MRI SCANS: The core facility has recently begun scanning fixed brains ex-vivo. By scanning brains for long periods of time, in some cases up to 72 hours, it is possible to gain high resolution and signal-to-noise, as well as a sampling of different diffusion directions. The preparation of the fixed brain is challenging, and involves stabilizing the specimen in a suspension that has the same susceptibility as the tissue, but that does not emit an MRI signal. It also requires soaking the specimen for a period in gadolinium to optimize the proton relaxation time for the MR scanning. This approach has led to a number of very high quality samples for analyzing tracts in diffusion-weighted imaging. The NIF facility staff is presently writing two papers emerging from this research that we hope will impact the way people use and think about diffusion tensor imaging (DTI) results.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Scientific Cores Intramural Research (ZIC)
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Kaskan, P M; Costa, V D; Eaton, H P et al. (2016) Learned Value Shapes Responses to Objects in Frontal and Ventral Stream Networks in Macaque Monkeys. Cereb Cortex :
Chang, Catie; Leopold, David A; Schölvinck, Marieke Louise et al. (2016) Tracking brain arousal fluctuations with fMRI. Proc Natl Acad Sci U S A 113:4518-23
Papoti, Daniel; Yen, Cecil Chern-Chyi; Hung, Chia-Chun et al. (2016) Design and implementation of embedded 8-channel receive-only arrays for whole-brain MRI and fMRI of conscious awake marmosets. Magn Reson Med :
Reveley, Colin; Seth, Anil K; Pierpaoli, Carlo et al. (2015) Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography. Proc Natl Acad Sci U S A 112:E2820-8
Russ, Brian E; Leopold, David A (2015) Functional MRI mapping of dynamic visual features during natural viewing in the macaque. Neuroimage 109:84-94
Liu, Xiao; Yanagawa, Toru; Leopold, David A et al. (2015) Arousal transitions in sleep, wakefulness, and anesthesia are characterized by an orderly sequence of cortical events. Neuroimage 116:222-31
Liu, Xiao; Yanagawa, Toru; Leopold, David A et al. (2015) Robust Long-Range Coordination of Spontaneous Neural Activity in Waking, Sleep and Anesthesia. Cereb Cortex 25:2929-38
Monosov, Ilya E; Leopold, David A; Hikosaka, Okihide (2015) Neurons in the Primate Medial Basal Forebrain Signal Combined Information about Reward Uncertainty, Value, and Punishment Anticipation. J Neurosci 35:7443-59
Thomas, Cibu; Ye, Frank Q; Irfanoglu, M Okan et al. (2014) Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited. Proc Natl Acad Sci U S A 111:16574-9
Fukushima, Makoto; Saunders, Richard C; Leopold, David A et al. (2014) Differential coding of conspecific vocalizations in the ventral auditory cortical stream. J Neurosci 34:4665-76

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