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Watching the Brain Create Memories

The brain stores information in a cohesive way so that we can recall the myriad of details about an event: who was there, what music was playing, what the food smelled and tasted like, and how the occasion made us feel. These aspects of an event are bound into an integrated "memory trace" so that the whole event can be retrieved instantly. In order to store and retrieve information, the brain has to perform three functions. First, information that has been learned only moments earlier is captured in short-term memory. Second, the brain moves the information into long-term storage. Third, the brain has to be able to find and retrieve the memory on demand.

One of the brain regions involved in moving information from short-term memory to long-term storage is the hippocampal formation. Scientists have studied individuals who have had extensive damage to their hippocampal formation; the moment their attention is diverted, they have no memory of a conversation they've been having. A person with a malfunctioning hippocampal formation would still have lots of thoughts and would be able to perform activities, but wouldn't be able to form new memories or learn new facts.

Using functional MRI scans, Dr. Sperling has focused on a network of brain regions that are involved when a person is engaged in forming a memory. The scans clearly show that these regions engage in a finely tuned process in which one area turns on very rapidly when a person is learning something new. That region, the hippocampal formation, is responsible for binding new information together into a short-term memory, which can later be transferred into a long-term memory for storage in other brain areas. At the same time, other areas of the brain, in particular the parietal regions, must turn off so as not to interfere with the memory formation process. Later, when the person recalls a memory, the process is somewhat reversed. Many of the regions in the brain that were turned off during memory formation now turn on to retrieve the memory. This cycle of turning on and turning off, or activation and deactivation, as Dr. Sperling called it, happens all the time.

"When we look at the fMRI of a healthy person, we see that the memory network is carefully synchronized. The parietal regions are constantly turning on and off and working in coordination with the hippocampal formation. This network activity correlates with how well the person is able to perform the memory task."

In a person with Alzheimer's disease, the fMRI shows little or no activation of the hippocampal formation when the person is asked to learn something new. This correlates with pathological changes in the brain, as this area is among the first to be damaged in AD. Dr. Sperling explains that MRI scans of people with Alzheimer's disease show shrinkage, or atrophy, of the hippocampal formation as well as a thinning of the brain or loss of neurons in the parietal regions. The parietal regions are also especially vulnerable to the formation of beta-amyloid plaques in AD.

Dr. Sperling is now conducting fMRI studies that use face-name memory tasks to see whether beta-amyloid is causing these disruptions in the activation and deactivation process in people with early-onset AD, as well as to study those with MCI and normal memory function. While conducting an fMRI study, Dr. Sperling asks research volunteers to look at photographs of faces and learn to associate each face with a name. The name-face recognition task is particularly difficult for people with AD, which is why she chose it for the test. "If you want to determine whether someone is at risk for a heart attack, you put them on a treadmill and stress the system. We stress the brain with memory tests to see how it performs."

While lying in an fMRI machine, research volunteers are shown many pairs of face photos labeled with names. Thirty minutes later, they are shown the same faces with two name choices and asked to recall the name that goes with each face. This fMRI technique allows Dr. Sperling to see which parts of the brain are activated and deactivated during the exercise. A healthy person would quickly form the association between the photograph of a face with the name Derek, and the fMRI would indicate that normal hippocampal activation had occurred during that formation of Derek's face-name association. On the other hand, when a person with AD tries to learn the Derek face-name association, the fMRI scan shows little or no activity in the hippocampal formation and they might look at Derek's picture and say, "It could be Derek or Ian. I have no idea."

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Next: Hyperactive Hippocampal Formation

Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.