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

Alzheimer's Disease (AD)

A progressive degenerative disease of the brain that causes impairment of memory and other cognitive abilities.

Amyloid Precursor Protein (APP)

The larger protein from which beta-amyloid is formed.

ApoE Gene

A gene that codes for a protein that carries cholesterol to and within cells; different forms of the ApoE gene are associated with differing risks for late-onset Alzheimer's disease. This gene may be referred to as a risk factor gene or a "susceptibility gene" because one form of the gene, called APOE4, is associated with the risk of developing late onset AD.

Beta-Amyloid

Derived from the amyloid precursor protein and found in plaques, the insoluble deposits outside neurons. May also be called A-beta.

Beta-Amyloid Plaque

A largely insoluble deposit found in the space between nerve cells in the brain. The plaques in Alzheimer's disease are made of beta-amyloid and other molecules, surrounded by non-nerve cells (glia) and damaged axons and dendrites from nearby neurons.

Cognitive Reserve

The brain's ability to operate effectively even when some damage to cells or brain cell communications has occurred.

Dementia

A broad term referring to a decline in cognitive function that interferes with daily life and activities. Alzheimer's disease is one form of dementia.

Functional MRI (fMRI)

An adaptation of an MRI (see magnetic resonance imaging) technique that measures brain activity during a mental task, such as one involving memory, language, or attention.

Hippocampal Formation

A structure in the brain that plays a major role in learning and memory and is involved in converting short-term to long-term memory. Also called the hippocampus.

Inflammation

The process by which the body responds to cellular injury by attempting to eliminate foreign matter and damaged tissue.

Insulin Resistance

A condition in which the pancreas makes enough insulin, but the cells do not respond properly to it; characterizes and precedes type 2 diabetes.

Magnetic Resonance Imaging (MRI)

A diagnostic and research technique that uses magnetic fields to generate a computer image of internal structures in the body.

Mild Cognitive Impairment (MCI)

A condition in which a person has cognitive problems greater than those expected for his or her age. Amnestic MCI includes memory problems, but not the personality or other cognitive problems that characterize AD.

Neurodegenerative Disease

A disease characterized by a progressive decline in the structure and function of brain tissue. These diseases include AD, Parkinson's disease, frontotemporal lobar degeneration, and dementia with Lewy bodies. They are usually more common in older people.

Oligomers

Clusters of a small number of beta-amyloid peptides.

Oxidative Damage

Damage that can occur to cells when they are exposed to too many free radicals.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Pittsburgh Compound B (PiB)

The radioactive tracer compound used during a PET (see Positron Emission Tomography) scan of the brain to show beta-amyloid deposits.

Synapse

The tiny gap between nerve cells across which neurotransmitters and nerve signals pass.

Tau

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Tangles

A protein that helps to maintain the structure of microtubules in normal nerve cells. Abnormal tau is a principal component of the paired helical filaments in neurofibrillary tangles.

Memory

Normal Aging

Genetic Risk Factor

Dominant and Recessive Genes

Genes and Proteins

Protein-Misfolding Disease

Cholesterol

Biomarkers

Disease-Modifying Drug

Transgenic Mice

An animal that has had a gene (such as the human APP gene) inserted into its chromosomes for the purpose of research. Mice carrying a mutated human APP gene often develop plaques in their brains as they age.

Pathology

Microglia

Insulin & Insulin Resistance

Susceptibility Gene

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Susceptibility Genes

A variant in a cell's DNA that does not cause a disease by itself but may increase the chance that a person will develop a disease.

Genome-Wide Association Study

Vascular Disease

Genetics

Genetics

Normal Aging