The expansion of magnetic resonance imaging in the past decades had greatly changed the way scientists, clinicians, and the public view the human brain. At its essence, MRI is based on the nuclear spin properties of water protons that compose various different brain tissues. Through the resonance properties of these protons, and the differential influence of the surrounding tissues, these spin properties can be probed and, ultimately, assembled into images that directly reflect the anatomical structure. Moreover, the blood content and oxygenation can influence these images, allowing one to locally estimate neural activity at each moment in time. The latter technique, functional magnetic resonance imaging (fMRI) is presently the most efficient and powerful way to study activity in the human brain. Its use has provided a grip on studying the physiological basis of human cognitive processes previously though out of reach. Importantly, it allows us to study the function and dysfunction of the brain in psychiatric diseases, with the hope of deepening our understanding of their causes. The core facility called the Neurophysiology Imaging Facility (NIF) combines electrophyisology and fMRI studies, along with neuropharmacological and ablation studies.
The aim of this combined approach is to provide a description of the anatomy and physiology of the primate brain that is more detailed and comprehensive than can currently be achieved with noninvasive imaging approaches in the human. In many cases, rather different types of experiments are carried out simultaneously. For example, in a recent study, we carried out electrophysiological and fMRI recordings simultaneously in awake animals. In another, neuropharmacological manipulation was combined with targeted ablations and fMRI in behaving animals. In order to achieve these experiments, the NIF facility creates and distributes custom-made equipment tailored for individual primate imaging experiments. As a centralized core facility, the NIF offers services and products to a wide range of investigators in each of the three sponsoring institutes (NIMH, NINDS, and NEI). 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. The facility thus provides users with these and other critical components of monkey fMRI, allowing them to initiate their studies with minimal development on their part. The scanning routine in the NIF facility entails three 3-hour slots per day, some of which are devoted to high-resolution anatomical scanning, which allows investigators to determine the position of their electrodes, perform surgical planning, and evaluate the spread of pharmacological agents. The majority of the scans are reserved for functional imaging in awake and behaving animals. The routine combination of fMRI and invasive techniques in awake, behaving monkeys makes the NIH Intramural Research Program a unique site to perform nonhuman primate research. NIH investigators that use the NIF core facility are studying a wide range of topics related to basic neurological function, motivation, decision-making, emotion, and depression. Recently, work in the facility has also been directed toward the development and optimization of diffusion weighted imaging (DWI), which is based on the asymmetric diffusion of water molecules in white matter tracts. One version of this method, diffusion tensor imaging, or DTI, is currently very popular in the human neuroimaging community, since it allows for an estimation of structural connections between brain areas. In the NIF facility, we are presently exploring the limits of DWI using fixed brain specimens of both rhesus and marmoset monkeys. The brains are scanned ex-vivo for up to four days continuously, allowing for unprecedented spatial resolution and angular resolution. We are presently conducting a study to understand the role that these factors have on tractography, or the estimation of fiber pathways. This study could have important implications for a range of human and clinical studies for which the trade of between patient comfort and spatial resolution is important. It can also shed light on the overall accuracy of the DTI method.
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