As the technology of magnetic resonance imaging (MRI) improves, and as scanners become more prevalent across the world, both structural and functional imaging have become a central part of brain research in nonhuman primates. This is because having a precise 3D map of structures or activity in the brain leads to the most efficient and targeted research, where activity in a given portion of the brain is to be measured, inhibited, or otherwise manipulated. The parallelism with human MRI methods also pushes the results from nonhuman primates to more directly applicable and translatable to humans. The NIF facility at the NIH strives to make both structural and functional imaging feasible and fluid for any laboratories on the NIH campus interested in applying these methods. We offer high resolution anatomical scans, diffusion imaging, as well as comprehensive functional imaging. Functional MRI in nonhuman primates is notoriously difficult, and is usually carried out by scientists with expertise in other domains. Moreover, fMRI experiments in nonhuman primates are most valuable and also most difficultwhen combined with other methods. Thus one of our main goals is to lower the many conceptual and practical barriers involved in the scanning itself so that researchers can pursue combinatorial methods. Our staff assists in any of these scans, and further works to help scientists gain autonomy in conducting their own experiments, thus after a stint of research in the NIF facility many trainees know the basic principles of MRI and are able to operate the scanner. Functional MRI (fMRI) allows researchers to visualize activity patterns within the brain of an awake human or animal. This approach to neuroscience often involves mapping the responses for one type of sensory stimulus relative to that for another. This straightforward type of mapping, which is routine in humans, is also routine in nonhuman primates as long as the experimental components and infrastructure are in place. There are many analysis steps between the acquisition of raw MR signals and the scientific interpretation of the measured neural signals. This is particularly true for functional MRI (fMRI), where activity maps are generated based upon the evaluation of time varying intensity values throughout the brain from a series of MR volumes. Most neuroscience researchers are not experts in the physics or engineering aspects of MRI and thus rely heavily on experts in these domains to develop and maintain the best scanning environment possible. Thus, MRI experiments are typically done in the context of a core imaging facility. In animal studies, the challenges of MRI are compounded, as technical issues such as the production of specialized radiofrequency (RF) coils and practical skills such as surgery and the animal's behavioral training become additional factors. Animal scanning is typically combined with other procedures such as pharmacological manipulation or simultaneous electrophysiological recording, often further complicating the imaging procedure. Overcoming these obstacles, however, can be of enormous value, since the capacity to map activity over the entire brain is especially powerful when combined with well-conceived manipulations or measurements. In the Fall of 2018, the 4.7T vertical scanner in the Neurophysiology Imaging Facility will be joined by a 3T horizontal scanner. This combination will allow for a spectrum of different scanning possibilities for researchers at the NIH, ranging from routine anatomical scans to intricate, multimodal fMRI projects. These two scanners, together with Dr. Afonso Silvas neighboring 7T smaller bore scanner, all sit in the annex of Building 49, to our knowledge represent the largest concentration of primate-designated scanners in the world. These scanners serve all of the NIH, and will play an increasingly important role for biomedical and disease research in nonhuman primates. The arrival of the new 3T scanner will provide needed additional scanning time for our users, will centralize much of the anatomical scanning, and will accommodate the needs of two newly hired principal investigators. It will also provide for a longer-term transition to replace the 4.7T vertical scanner with a cutting-edge system in the future. Five staff members including Dr. Leopold, each from a different scientific background and with different skills, aim to provide the most efficient functional scanning possible for a broad range of investigators. Many users of the facility focus only on structural scanning, whereby the staff takes over most of the procedure and the scientist provides information about the target sites and basic scanning requirements. This approach is widely used to identify electrophysiological target sites, the position of indwelling microelectrodes, and evaluate experimental precision of a brain manipulation such as an injection. One particularly valuable use of structural imaging is the direct comparison of electrical recording sites with foci of fMRI responses in the context of a cognitive task. There are a range of contrast options, including diffusion weighted scans that can identify features in the white matter, or provide the basis for tractography. We have also recently purchased a computerized tomography (CT) machine to reside in the facility, and to serve as part of a pipeline to further improve surgical accuracy for a wide range of users. For functional scanning, much of the work is done by scientists in individual laboratories, which the NIF staff train to become largely autonomous in their experiments. 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 procedures, such as microelectrode recordings or pharmacological inactivation, or cortical ablation.. 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, guidance in the initial processing steps, and server machines for full data analysis. The NIF staff spends a relatively small fraction of its time carrying out research related to MRI itself. In the past several years, we have focused on completing studies related to diffusion tractography. Dr. Frank Ye scanned several ex-vivo brains and, in a highly collaborative effort with other groups inside and outside the NIH, we are continuing to study (1) the neuroanatomical basis of diffusion tractography, and (2) comparative fiber pathways across species (Takemura et al., 2017). In addition, we have recently completed studies on the role of the basal forebrain in resting state spontaneous fMRI signals (Turchi J Chang C et al., 2018; Liu X et al., 2018), as well as collaborative work involved in atlases, templates, and data sharing (Liu C et al., 2018; Seidlitz et al., 2017; Seidlitz et al., 2018; Milham et al., 2018). At present, research in the facility is focused on the design and testing of implanted radiofrequency coils, with the hope that this method can become routine for users seeking to obtain higher signal-to-noise images. Other research lines in the facility involve the development of scanning with newly available contrast agents.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Scientific Cores Intramural Research (ZIC)
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Ghazizadeh, Ali; Griggs, Whitney; Leopold, David A et al. (2018) Temporal-prefrontal cortical network for discrimination of valuable objects in long-term memory. Proc Natl Acad Sci U S A 115:E2135-E2144
Seidlitz, Jakob; Sponheim, Caleb; Glen, Daniel et al. (2018) A population MRI brain template and analysis tools for the macaque. Neuroimage 170:121-131
Bogadhi, Amarender R; Bollimunta, Anil; Leopold, David A et al. (2018) Brain regions modulated during covert visual attention in the macaque. Sci Rep 8:15237
Turchi, Janita; Chang, Catie; Ye, Frank Q et al. (2018) The Basal Forebrain Regulates Global Resting-State fMRI Fluctuations. Neuron 97:940-952.e4
Liu, Xiao; de Zwart, Jacco A; Schölvinck, Marieke L et al. (2018) Subcortical evidence for a contribution of arousal to fMRI studies of brain activity. Nat Commun 9:395
Liu, Cirong; Ye, Frank Q; Yen, Cecil Chern-Chyi et al. (2018) A digital 3D atlas of the marmoset brain based on multi-modal MRI. Neuroimage 169:106-116
Takemura, Hiromasa; Pestilli, Franco; Weiner, Kevin S et al. (2017) Occipital White Matter Tracts in Human and Macaque. Cereb Cortex 27:3346-3359
Reveley, Colin; Gruslys, Audrunas; Ye, Frank Q et al. (2017) Three-Dimensional Digital Template Atlas of the Macaque Brain. Cereb Cortex 27:4463-4477
Papoti, Daniel; Yen, Cecil Chern-Chyi; Hung, Chia-Chun et al. (2017) Design and implementation of embedded 8-channel receive-only arrays for whole-brain MRI and fMRI of conscious awake marmosets. Magn Reson Med 78:387-398
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

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