The advent of human fMRI has changed the focus of modern neuroscience, highlighting processes in the human brain. This macroscopic description of brain function is highly useful for addressing large-scale processes, and the extension of neuroscience to humans has been critical for learning about brain function, and disseminating the importance of neuroscientific research to the general public. At the same time it is both desirable and important to be able link patterns of fMRI activation, which are mediated through changes in blood flow, to the underlying electrical neural circuits that process sensory information and generate behavior. A large portion of our understanding of the primate brain has arisen not from studying humans, but from directly examining the activity of neurons in the brains of animals, and in particular monkeys. Critical for understanding the translation between fMRI and neural responses is therefore to establish correspondence between the fMRI and neural signals in monkeys. The Neurophysiology Imaging Facility (NIF) core offers a complete program by which investigators in each of the three sponsoring institutes (NIMH, NINDS, and NEI) may test awake behaving monkeys for functional signals in their brains.? ? In its functional program, the NIF concentrates on functional imaging in monkeys that are also enrolled in an electrophysiology experimental program. This has required a large amount of development, requiring MR-compatible chairs and restraint devices, reward delivery, and response keys. The benefit of this approach is that trained animals can easily be tested on alternate days in either the neurophysiology or fMRI environment. Initial work in the facility has shown that this is fruitful, as three studies are nearing completion, with two of them specifically relying on testing monkeys with both techniques. The merits of combining techniques include (1) localizing activity for targeted electrode recordings, (2) evaluating the equivalence of neural and fMRI signals in the context of a particular sensory or behavioral paradigm, and (3) basing comparisons between fMRI and electrophysiology data upon within-subject differences rather than between-subject averages. ? ? In addition, it is possible to perform simultaneous microelectrode and fMRI recordings inside the scanner bore. This technique is being used in the facility to examine the covariation of activity in different states of arousal, a method used to infer principles of functional connectivity in the monkey brain. The use of a neural reference in the monkey provides a cleaner and potentially more meaningful signal than can be attained in humans, with each element of fMRI signal fluctuation tied specifically to underlying neural events. At present, the underlying neural basis of functional connectivity in humans is largely unknown, and work in the NIF aims to provide a clearer picture of how information in large-scale brain networks might be integrated.? ? Structural imaging is another main goal of the NIF core facility, and in the last year we have expanded our sphere of service to the greater NIH community. In the facility, high resolution scans have been optimized in their contrast for visualizing anatomical features of interest. Anatomical imaging is carried out in both the awake and fully anesthetized animal preparation. In addition, the facility offers a number of techniques to electrophysiologists in order to facilitate targeted microelectrode recordings. First, a frameless stereotaxy system permits surgical approach to any target from any angle, allowing for a complete evaluation of potential trajectories of interest, as well as structures to be avoided. This approach is used regularly by users of the facility, and has contributed to the highly reliable targeting of deep cortical and subcortical structures.? ? A great advantage of using magnetic resonance imaging in monkeys is the capacity to combine MR measurements with invasive techniques. One particularly useful technique is injection of either MR-visible or neuroactive substances into the brain prior to imaging. In the NIF facility, we offer the capacity to inject a number of substances into the brain, ranging from contrast agents such as Gadolinum, to anatomical tracers such as manganese chloride, to neurotransmitter analogs and blockers. Injections are typically performed through a previously implanted cannula with the animal either anesthetized or awake. Locally injected contrast agents can be used to visualize the spread of a co-injected agent in the neuropil. Anatomical tracers can be used to identify polysynaptic neural tracts emanating from the injection point, which might, for example, correspond to a region of functional activation. Neurotransmitter analogs can be used to locally activate or inactivate a structure, the effect of which can then be monitored by monitoring the fMRI time series over the entire brain.? ? In addition to serving the needs of the NIH non-human primate imaging community, the NIF is continually upgrading and developing its cutting edge 4.7 Vertical monkey scanner. Development in the past year have included the development of roughly a dozen RF coils to accommodate different scanning challenges. New pulse sequences have additionally been developed, published, and offered to the MR-imaging community. In the coming year, the magnet will receive an upgrade, which maintain its position at the forefront of monkey imaging. Specifically an 8-channel system will replace the 1-channel system, leading to a great improvement in imaging quality, which translates to more refined knowledge about brain structure and activity. All innovations on the side of hardware development, pulse sequencing, other technical milestones, and the development of analysis software, are immediately made available to the entire NIH community for use in primate imaging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002899-01
Application #
7594621
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$825,232
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code