CONTACT: Stanford University News Service (650) 723-2558
Scientists at Stanford have distinguished between clusters of neurons just inches apart that are involved in two different aspects of human memory, according to a study published in the April 11 issue of Science.
Using the non-invasive technique of functional magnetic resonance imaging (MRI), psychology Professor John Gabrieli and his colleagues found more activity in a posterior region of the brain's hippocampus when people were trying to encode information into memory, and more activity in an anterior region when they were trying to retrieve previously learned information from memory. Encoding and retrieving new information is fundamental to learning and is believed to be one of the first memory activities affected by Alzheimer's disease.
Gabrieli, who studies the neural basis of memory, perception and cognition, conducted the research with graduate student James Brewer, research associate John Desmond and Gary Glover, a professor in the department of radiology at the Stanford School of Medicine.
Fig. 1. Images were used to select eight 7-mm contiguous sections, shown as lines, that covered the hippocampus in a plane perpendicular to its long axis. Medial temporal-lobe activations associated with the retrieval task were found in anterior sections (shown in green) and activations associated with the encoding task in posterior sections (shown in red).
The researchers used functional MRI to obtain thousands of images of the brain's temporal lobe while individuals with normal memory skills were performing different memory tasks. Functional MRI can be used to compare the flow of blood oxygen to various parts of the brain in order to tell which neurons are more activated at a given time. While the technique cannot be used to see blood flow to individual nerve cells, it can distinguish neural activity at locations separated by as little as one or two millimeters about a half to three-quarters of an inch. The entire memory system studied is about the size of a golf ball and is made up of a number of different parts that differ in their cell architectures and connections.
In one part of the study, adults were shown drawings of common objects and animals the day before and a half hour before imaging began. While being imaged, they were shown words and asked to squeeze a bulb filled with air when they saw the name of an object or animal they had previously seen in the drawings a task that requires retrieval of information from memory. In analyzing the MRI images, the researchers found more brain activation focused in the subiculum of the hippocampus when people retrieved memories of the drawings than when they were shown words for objects not seen before.
Medial temporal-lobe regions significantly activated in the retrieval and encoding memory tasks in individual subjects; each column depicts two oblique sections from one subject. Colored pixels exceeded the statistical threshold and were overlaid on corresponding anatomy images. Functional maps were normalized and linearly scaled in each section such that the lowest significant z-scores (1.96) appear in dark red and the highest in bright yellow/white. The left side of each picture is the left side of the brain. The top row shows activations in the subiculum during the retrieval memory task that were greater for words corresponding to previously seen than unseen line drawings (Subjects 1, 2 and 3) or greater for line drawings corresponding to previously seen than unseen words (Subject 4). Sections, from left to right, correspond to the second, third, fourth and fourth locations in Fig. 1. The bottom row shows activations in the parahippocampal cortex during the encoding memory task that were greater for novel than for repeated color scenes (Subjects 1, 2 and 3) or greater for novel than for repeated line drawings (Subject 4). Sections for Subjects 1, 2 and 3 correspond to the fifth location in Fig. 1, and the section for Subject 4 corresponds to the sixth.
In another part of the study, individuals were shown color pictures of indoor and outdoor scenes as their brains were being imaged. They were asked to remember details of the indoor scenes for a later memory test. Many photographs were repeatedly shown but others were shown only once. When individuals were encoding novel information color photographs not previously seen activation was greatest in a posterior location known as the parahippocampal cortex.
Researchers have long suspected that different structures in the brain's medial-temporal memory system specialized in different memory tasks, but until now the only experiments that have been able to establish such specialization were on monkeys and rats.
"The hippocampus is really a set of highly interconnected structures, so it has been hard to tell which one plays what role in memory," Gabrieli said. "With Alzheimer's disease, or other lesions, such as a stroke, many of the structures tend to get damaged together."
In graduate school at MIT, Gabrieli worked with "HM," a man often mentioned in textbooks because his medial-temporal memory system was damaged in such a way that he remained intelligent and perceptive, but he could not remember new information from one hour to the next. "From HM, we learned that the medial-temporal lobe memory system is essential for learning new information, but nobody has been able to say much about how this system supports memory," Gabrieli said.
Functional MRI, as a non-invasive imaging procedure, provides a relatively easy and inexpensive tool for neuroscientists to investigate specialization in many brain functions. Gabrieli, for example, is using the technique to study stroke patients and children with attention deficit disorder. Two of his colleagues in psychology, Brian Wandell and David Heeger, have used it to investigate the visual perception system. In addition to aiding general understanding of the brain, such studies eventually could lead to treatments for various types of diseases or injuries or for less invasive ways to perform tests such as those used prior to some types of brain surgery.
Gabrieli also is participating in a longitudinal study to look for early signs of Alzheimer's Disease in the brain's memory system. Priests and nuns in several states have volunteered for MRI brain imaging annually. If some later develop symptoms of the disease, the scientists will be able to look back at images for the earliest signs of it in the brain.
"Autopsies of Alzheimer's patients have indicated that the subiculum portion of the hippocampus is affected early and severely in the disease," Gabrieli said. "Alzheimer's patients have great difficulty in gaining new information."
If the disease can be detected before people show behavioral symptoms such as poor memory, currently ineffective treatments may prove effective, he said. "Most of the drugs that we've looked at for treating Alzheimer's disease don't work now, and one of the reasons may be that the disease is just too far along by the time we detect it."