Nearly every university has several investigators that use fMRI to study the brain. As a noninvasive means of monitoring brain activity in humans, fMRI has changed the face of systems neuroscience, and has emphasized the importance of considering the whole brain when tackling problems such as perception, reward, and decision making. Yet the relationship between the fMRI signal and underlying neural responses is tenuous, and sometimes paradoxical. The great advantage of studying fMRI in monkeys, as in the Neurophysiology Imaging Facility (NIF), is that imaging experiments can be combined with invasive techniques, such as pharmacological manipulations and neurophysiological recordings. ? ? Functional MRI activation is mediated primarily through changes in blood flow, and these changes are presumed to be initiated by the activity of underlying electrical circuits that process sensory information and generate behavior. The specific link between neural activity and the vasculature is, however, a topic of intensive research and debate. 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.? ? Considerable effort was made to establish a fluid means of performing 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. ? ? Combining noninvasive fMRI scanning with invasive procedures is one of the principal advantages of monkey fMRI. We have taken three basic approaches to providing the NIH nonhuman primate imaging community with means of combining invasive techniques with imaging. ? ? (1) Neuropharmacology. Studies in the NIF have inactivated portions of the brain locally using a GABA agonist (muscimol) while awake animals perform tasks inside the scanner, and then examine the changes in functional activity in other brain regions. This has been an effective tool, permitting the unprecedented visualization of global patterns of activity following local inactivation. ? ? (2) Simultaneous microelectrode recording. We have been using implanted multicontact electrodes to monitor neural activity in different layers during functional scanning. This has permitted us to study stimulus-based activation, as well as spontaneous covariation in the activity fluctuations of in neural and fMRI signals. ? ? (3) Electrical microstimulation inside the magnetic bore. This technique has recently been used to infer structural and functional connectivity between areas, with functional activation far away from the site of stimulation indicating such a connection. ? ? Structural imaging is a primary service 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.? ? Finally, we have recently completed an upgrade of our 4.7T vertical monkey scanner to an 8-channel parallel system, which will permit unprecedented imaging for both structural and functional purposes. To match the evolving needs of the user community, the NIF core is developing new hardware, such as the many RF coils, implants, and holding devices required by various users. We make each of our techniques, pulse sequences, coil designs, and analysis methods immediately available to our uses, as well as to the larger fMRI community.
| Xiang, Qing-San; Ye, Frank Q (2007) Correction for geometric distortion and N/2 ghosting in EPI by phase labeling for additional coordinate encoding (PLACE). Magn Reson Med 57:731-41 |
