Noninvasive functional MRI in alert monkeys

Abstract

Functional magnetic resonance imaging (fMRI) is now widely used to study human brain function. Alert monkey fMRI experiments have been used to localize functions and to compare the workings of the human and monkey brains. Monkey fMRI poses considerable challenges because of the monkey's small brain and naturally uncooperative disposition. While training can encourage monkeys to be more obliging during scanning, the usual procedure is to hold the monkey's head motionless by means of a surgically implanted head post. Such implants are invasive and require regular maintenance. In order to overcome these problems we developed a technique for holding monkeys' heads motionless during scanning using a custom-fitted plastic helmet, a chin strap, and a mild suction supplied by a vacuum blower. This vacuum helmet method is totally noninvasive and has shown no adverse effects after repeated use for several months. The motion of a trained monkey's head in the helmet during scanning was comparable to that of a trained monkey implanted with a conventional head post.

Figure 1

The vacuum helmet (left) and an alert monkey (right) sitting calmly, in the helmet, ready to be scanned.

Figure 2

Translation in mm (left) and rotation in degrees (right), normalized to the position at the beginning of each scan, during a single, typical, scan session for two vacuum-helmeted alert male monkeys (red & green traces) and a head-post restrained alert male monkey (black traces). X-axis is image number; one image was taken every 2 seconds. Most of the large position shifts occurred between scans; each scan onset is indicated by an arrow.

Figure 3

Average brain movement, normalized to the position at the beginning of each scan, over the first 100 seconds of each scan for three alert monkeys ± standard deviation, averaged over 200 scans; for the two helmeted male monkeys in red & green and the head-post restrained male monkey in black.

Figure 4

Translational movements exhibited by one alert female monkey restrained using a helmet (red traces) or by a head-post (black traces). Left, movements during 20 consecutive 100 second (50 images) scans each during two different scan sessions, normalized to the position at the beginning of the session. Right, average movement, normalized to the position at the beginning of each scan, ± standard deviation for all 20 scans under each restraint condition.

Figure 5

Semi-inflated (top-left) and flattened (top-right) brain maps showing significant activation in response to horizontal (red) and vertical (blue) meridian stimuli viewed by an alert monkey non-invasively restrained by a vacuum helmet. (bottom) Time course of the mutually exclusive signal changes ± standard deviation in response to alternating horizontal (bottom-left) and vertical (bottom-right) meridians from two 4.5 × 4.5 × 4.5 mm ROIs as indicated calculated from 20 scans obtained in a single scanning session. Activations are both large and negative, compared to BOLD signal, because the monkey was injected with the iron oxide contrast agent Feraheme prior to scanning; the agent causes a decrease in the baseline and an inversion of signal (Leite et al. 2002). The functional activation maps were overlaid on the F99 atlas in Caret (Van Essen 2002); http://sumsdb.wustl.edu/sums/macaquemore.do. Areal borders were drawn by hand according to alternating meridians.

Figure 6

Anatomical scans for monkey F1obtained during one 4 minute anatomical scan using the same helmet and coil as was used for the functional imaging. The section plane was coronal, so any changes in position during the scan should result in blurring or shifts in position between anterior and posterior sections, yet no difference in resolution is apparent between the coronal and the horizontal or sagittal reconstructions.