A sharper look at the brain

Picture credit: Max Planck Institute for Biological Cybernetics, Tübingen Picture caption: Cross section of a monkey brain. The red and yellow areas are the brain regions activated by a visual stimulus. Full size image available through contact

Thanks to a dramatic improvement in imaging techniques it is now possible to generate high-resolution pictures of the monkey brain in a quality never seen before. A research group led by neurophysiologist Prof. Nikos Logothetis of the Max Planck Institute for Biological Cybernetics and physician Prof. Dr. Heinz Guggenberger of the Eberhard Karl University (both in Tübingen, Germany) was the first ever to successfully use the so-called fMRI technique (from functional magnetic resonance imaging) to produce detailed pictures of active brain regions in monkeys which have been anesthetized but are still capable of perception (nature neuroscience, Vol. 2, No. 6, June 1999). Until now, many scientists were convinced that it would be impossible to gather such images from anesthetized monkeys.

The fMRI technique uses a strong magnetic field to detect brain regions which are active and thus more strongly perfused. It promises new impetus for the area of brain research. fMRI makes it possible to pinpoint the precise regions of the monkey's visual cortex (that region of the cerebral cortex responsible for sight) where optical stimuli are processed. The non-invasive measurements are carried out under anesthesia conditions that meet the most up-to-date standards in human clinical medicine. The eyelids are held open artificially so the animals can see the presented test pattern. At the same time, constant irrigation prevents any damage to the eyes. The monkey wakes up and is fully conscious an average of 15 minutes after the experiment. The new technique places much less strain on the animal than conventional methods and makes it unnecessary to put them to sleep after the experiment.

The improved method made it possible to visualize brain volumes as small as 0.5 microliters in anesthetized monkeys and 2 microliters in a control group of alert monkeys. (One microliter is one millionth of a liter.) This is the highest resolution ever achieved in pictures of the primate brain. The magnetic resonance "shots" are taken while the monkey is viewing rotating patterns or pictures of conspecifics. The anesthetized macaques are immobilized in an upright, seated position inside the magnetic resonance tube with the aid of bandages and supports. Special measuring signals scan the brain one "slice" at a time. All of these cross sections are then reassembled by the computer to generate an image of the entire organ.

Although the laboratory animals were anesthetized, Logothetis and coworkers repeatedly observed clearly visible activities in brain regions where optical stimuli are processed. The scientists found elevated oxygen levels in the lateral geniculate body (a thalamic structure of the brain), the primary visual cortex V1 and a number of so-called extrastriate visual regions of the cortex. These oxygen hot spots are produced by the increased blood circulation in the active regions of the brain. The nerve cells of the superior temporal sulcus (STS), which respond to faces, could also be activated in the same manner. Similar but less precise patterns were found by the scientists in alert animals especially trained for this experimental set-up.

Picture credit: Max Planck Institute for Biological Cybernetics, Tübingen Picture caption: Reconstruction of a head divided into 3 layers - the subject is viewing a visual stimulus. In the lower section one can see how the x-shaped optic nerve transmits the impulse to two dot-shaped yellow centers and to the primary visual cortex V1 at the edge of the brain. Full size image available through contact

Conventional brain studies on monkeys have always been hindered by the fact that the animals seldom remain still during the measurements, thus distorting the results with movement artifacts. This made it necessary to invest substantial effort into training the monkeys to look at objects from a reclining position without moving. In addition, scientists have also believed until now that anesthetics would have a profound effect on brain activity in monkeys and that the use of anesthetics must be strictly avoided while taking fMRI pictures. The Tübingen group's results disprove these assumptions. Carefully applied, precisely dosed anesthetics leave the brain areas involved in processing optical stimuli active. "Because these carefully anesthetized animals are in such an incredibly stable physiological state," says Prof. Nikos Logothetis, "the experimental results from anesthetized monkeys are far more exact than those from alert animals."

Bruker Medizintechnik, a manufacturer specialized in magnetic measurement equipment, custom-built a machine with a magnetic field strength of 4.7 tesla especially for these experiments. The resolution of magnetic techniques such as fMRI, i.e. the ability to visualize even very fine structures, increases with the strength of the field. The field strength of the Tübingen machine is approx. 3 times greater than that of machines currently being used to examine humans, which gives it a corresponding boost in performance.

A substantial share of our still fragmentary knowledge about the physiological processes involved in sight comes from studies on monkeys. Their visual system displays great similarities to that of humans. The anatomical and functional organization of the brain is similar in both, and visual performance is also comparable in humans and monkeys. Monkeys have excellent color, movement and depth vision. Their visual acuity and contrast sensitivity, too, are close to those of humans, as are their ability to recognize objects and their eye movement patterns. Because of all these similarities, research on monkeys can help us better understand how we ourselves perceive objects, visually "learn" them, and then recognize them again later. "The improved fMRI technique," states Prof. Logothetis, "is an excellent complement to other brain research techniques such as positron emission tomography (PET) or electrode measurements. It opens up new avenues to a closer look at the functional anatomy of the brain."

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