LONDON ¿ Exactly how the brain allows us to remember what we had for breakfast this morning, let alone the sandcastles we built on vacation at the age of nine, is a mystery ¿ and likely to remain one for a long time. Nevertheless, advances in imaging techniques making it possible to see which parts of the brain ¿light up¿ during particular mental functions have allowed researchers to make strides in determining which areas of the brain take part in which thought processes.

Researchers in the U.K. have now employed a method called functional magnetic resonance imaging (fMRI) in a study examining which parts of the brain are involved in encoding new memories. Magnetic resonance imaging makes it possible to see which areas of the brain are more active during performance of particular types of cognitive operations, such as imagining, paying attention or experiencing emotion.

Professor Ray Dolan and colleagues in the Wellcome Department of Cognitive Neurology, at the Institute of Neurology in London, decided to use fMRI to examine how the part of the brain called the hippocampus responds in people given stimuli which were either novel or familiar. As they report in their paper in the March Proceedings of the National Academy of Sciences, they found that the activity in the left anterior hippocampus was significantly increased when subjects were presented with novel stimuli. Conversely, as the subjects became familiar with the stimuli, activity in the posterior part of the hippocampus increased.

The title of their paper, ¿Segregating the functions of human hippocampus,¿ summarizes their main finding: that the anterior and posterior parts of the hippocampus have different functions.

Bryan Strange, a Ph.D. student working with Dolan, and first author of the paper, told BioWorld International: ¿We know that the hippocampus is involved in memory, but we don¿t understand its precise psychological role. In order to understand memory disorders, you have to understand first how the hippocampus works in the healthy brain. We hope that this kind of work will ultimately be of benefit in understanding, for example, how damage to the hippocampus due to lack of oxygen, such as during a heart attack, results in memory loss, or how Alzheimer¿s disease ¿ in which the hippocampus is particularly heavily affected ¿ causes loss of memory.¿

Hippocampus May Help Process New Stimuli

The hippocampus, which is an evolutionarily ancient part of the brain, is a swelling in the floor of the lateral ventricle. One of the earliest clues to its function came from a patient known as H.M., who had had the anterior hippocampus removed in an attempt to treat severe epilepsy. This 1957 case study reported that H.M. lost the ability to form new memories following the surgery, but could recall memories acquired before the operation.

More recently, various pieces of evidence have supported the view that the hippocampus may be involved in processing new stimuli. For example, work in rats and monkeys, involving recording the electrical activity of individual neurons, has shown that cells in the hippocampus respond when the animals are presented with novel items.

A few studies have also been carried out in humans who have had electrodes implanted surgically into their brains, usually to try to localize areas of the brain affected by epilepsy. These have shown that the hippocampus responds in different ways to novel and familiar stimuli. Other studies of humans have examined the wave form of the electroencephalogram (a non-invasive technique in which electrodes are attached to the scalp) and shown that a distinctive ¿brainwave¿ pattern occurs when the subject is presented with novel stimuli. But this pattern is absent if the hippocampus is damaged.

In 1997, Dolan and Paul Fletcher, formerly in the Wellcome Department of Cognitive Neurology, published a study in Nature which showed that the hippocampi of human subjects were at their most active when the subjects were presented with novel pairs of words after having become familiar with a list of word pairs. This study measured brain activity with positron emission tomography.

Left Anterior Region Targeted

Dolan¿s group decided to further explore this finding, using fMRI. The test they used involved presenting the subjects with strings of letters, such as JMQH. After each presentation, the subjects had to press a button saying if the string was ¿true¿ or ¿false.¿ Although there were certain rules determining the right answer (such as that Q had to be followed by R, L or H, or that L could not follow M), the subjects were not told what these were and had to pick the rules up as the experiment progressed. They were able to do this because they were given immediate feedback about whether they had given the correct answer.

During the course of the experiment, the researchers introduced two different types of novelty. One was of a type which would not affect the feedback the subject received: it involved changing the font in which the letters were displayed. The other was ¿behaviorally relevant.¿ It involved a new string, of a type not seen before. The subjects therefore had to consider whether this set of letters fitted the rules, as far as they knew them, and again say if the string was true or false.

Strange explained: ¿We found an interesting dissociation. There was a significant increase in activity in the region of the left anterior hippocampus, when items were novel. This activation was attenuated as the subjects became familiar with both the font and the letter string. Conversely, the posterior hippocampus region became more active as the subjects became more familiar with the letter strings, but not with the font. So, it seems that there is a dissociation of function between the anterior and the posterior regions of the hippocampus.¿

It could be speculated, he added, that H.M. may have been unable to form new memories because he had had the anterior hippocampus removed, while familiar, well-rehearsed memories may have remained, because the posterior hippocampus was still intact.

Strange has already carried out further studies on novelty, but withheld comment on these until they are published. n