Probing the Mechanics Behind How We Remember

December is a time of memories. Scents of cinnamon and fresh evergreen evoke holidays past. Dangling mistletoe conjures up long-ago kisses. With each refrain of Christmas carols, words and music not heard for a year come tumbling back.

All animals, from the lowly sea snail to humans, have some form of memory. But people possess the remarkable ability to make a nearly infinite number of memory associations. It’s why the loss of memory--due to aging, illnesses such as Alzheimer’s disease or accidents--is so profoundly unsettling. And it’s why, as the Decade of the Brain draws to a close, neuroscientists are pressing to better understand this still-mysterious process.

“Every thought we have, every word we speak, every action we engage in--indeed, our very sense of self and our sense of connectedness to others--we owe to our memory, to the ability of our brains to record and store our experiences,” say neuroscientists Larry R. Squire and Eric Kandel in their book “Memory: From Mind to Molecules.” “Memory is the glue that binds our mental life, the scaffolding that holds our personal history and that makes it possible to grow and change throughout life.”

Parsing Memory’s Locator Points

Using a variety of sophisticated new imaging devices, researchers are beginning to understand some of neuroscience’s most central questions: How are memories organized in the brain? Is there a particular brain center for seemingly mindless daily habits, from climbing out of bed to brushing your teeth? How does the brain recall vivid details from a movie, a book or a painting? Where does the memory for recognizing a face exist?

“It’s a very difficult thing to find the anatomic parts of memory in the brain,” said Daniel Alkon, director of the Laboratory of Adaptive Systems at the National Institute of Neurological Disorders and Stroke. “We see a picture of our father’s face and hear his name and recall our relationship with him. But to find where that is stored [in the brain] is an incredibly difficult task.”

Until recently, memory research was largely confined to animals and to individuals in whom memory had begun to unravel. People suffering from amnesia, the aftermath of a stroke and various forms of dementia gave scientists rare glimpses into the mysteries of memory.

One of the most fascinating cases was a 9-year-old boy who cracked his head on the sidewalk after being knocked down by a bicycle. His misfortune turned into a lengthy, classic study that provided the first riveting proof that memory is not one single brain process.

The child suffered debilitating seizures and frequent blackouts. By age 27, he was so incapacitated that neurosurgeons removed part of his brain--the hippocampus and two areas known as the medial temporal lobes.

The operation, performed in the mid-1950s, cured the man’s seizures but left him unable to retain new information. Meals eaten, people met, even photos of himself as he aged held no meaning because he could not transfer them to his long-term memory. The man retained enough knowledge of language and life to hold a normal conversation. What he couldn’t recall--even a few minutes afterward--was having the conversation.

Yet the man could vividly remember events that occurred before the accident, and he could even learn some new skills.

McGill University psychologist Brenda Milner, who has studied the man for 40 years, concluded that he couldn’t retain new memories because he no longer had the medial temporal lobes and the hippocampus in his brain to store them. Yet since the man could recall events before his injury, Milner and her team determined that neither the temporal lobes nor the hippocampus could be the brain’s final storage sites for longer-term memories.

In healthy individuals, the hippocampus and the medial temporal lobes are at the heart of declarative memory. But the process of capturing and recalling information extends throughout the brain, often in milliseconds.

Each memory seems to be a compilation of tiny bits of information stored in a vast network of different cells. The simple ability to recall a phone number is believed to involve the activation of several thousand nerve cells, called neurons, distributed throughout the brain.

“Humans are in a class by themselves,” said Alkon. “The wiring inside the brain is designed to allow us at the flip of a coin or a snap of the fingers to connect or associate any bits of information with any other bit. We can do it lightning fast. In terms of learning new associations, most of what we do can be formed in fractions of a second.”

And the potential for storing long-term memories is thought to be nearly endless, given the multiple associations between cells. Each human brain contains an estimated 100 billion neurons, each capable of making up to 10,000 connections with other brain cells. The number of possible memories starts to approach the number of molecules in the universe, Alkon said.

An Arsenal of High-Tech Tools

Modern imaging techniques are enabling scientists to study the brain in ways once unimaginable and providing an understanding of the chemical processes that make memories.

With positron emission tomography and functional magnetic resonance imaging, for example, neuroscientists can pinpoint brain activity during different memory tasks.

At the National Institute of Mental Health, Alex Martin, chief of the section on cognitive neuropsychology, and colleagues James Haxby, chief of the section on functional brain imaging, and Leslie Ungerleider, chief of the Laboratory of Brain and Cognition, use these techniques to explore how the brain stores information.

The findings reveal a brain organized around the processes of learning, not the objects themselves, and by the way in which these objects are used. “A hammer, for instance, is stored in an area that involves motion, while the image of a cat is placed in a part of the brain that contains other visual shapes,” Martin said.

To identify an object, he said, “we instantly retrieve information by the features that define it. What does it look like? What color is it? How does it move or how do we manipulate it, if it’s a tool?”

For example, the studies found that verbs are stored in areas of the brain just in front of regions involved in the perception of motion. Colors of objects--the memory of a pencil’s bright yellow hue, for example--are stored next to the perception of color.

Thus a hammer is stored three ways in the brain: once for its form, once for its function or motion and once for the memory of the motor skill needed to use it. “We store these bits of information about objects near their features,” Martin said. “It’s all very logical.”

Memory Storage: a Multi-Site Process

But scientists are searching even deeper, seeking to unravel how individual brain cells store and share information. Last month, researchers at the University of Geneva in Switzerland announced that they had captured what appears to be the first electron micrograph image of the cellular changes involved in long-term memory. Reporting in the journal Nature, the team showed how the connections between two nerve cells in a rat’s brain change significantly when long-term memory is established.

In an alteration that is believed to occur across nearly all species from rat to human, the team found significant changes in the spiny dendrites that form at gaps between nerve cells called synapses. Scientists believe that this change facilitates a host of associations linking a particular memory with experiences, thoughts, emotions, sights, sounds and smells.

At the chemical level, memory storage seems to activate the nerve cell to start a cascade of reactions that can last a fraction of a second or linger for years, depending on the type of memory being stored. While much of this work has been conducted in sea snails, there’s evidence to suggest that the process applies to higher species, including people.

Alkon and his colleagues at the National Institute of Neurological Disorders and Stroke have found that the first change is in calcium, which floods into the neuron within milliseconds of the start of a memory task. This is one of the things that scientists believe happens when you look up a phone number for a restaurant and hold it in memory for just the short time it takes to place the call.

This ability “is what people refer to as working memory,” said Robert Desimone, director of NIMH’s Intramural Research Program.

But if you need to remember that phone number permanently, rehearsal is necessary, and it prompts an intricate series of reactions within the nerve cell.

Acuity of Interest Can Affect Retention

Why some memories are saved and others are simply discarded in healthy people appears to be determined in part by attention. Throughout the day, the brain is bombarded by thousands of pieces of information. Remembering every activity of every day would quickly overload neural circuits.

So the novelty of certain situations and the emotions and other sensory cues about them help dictate their importance and their storage in our memories. Vivid, emotional experiences appear to release chemicals in the brain that aid in the storage of information, Desimone said. “So, if I tell you, ‘I’m going to give you this Pizza Hut number and I want you to remember it,’ you probably would for a few minutes. But if I said, ‘Remember this number, or I will kill you,’ it might actually get stored right away in your long-term memory.”

Attention, whether prompted by fear or genuine interest, helps filter what is saved in memory, and for this reason, it has become one of the new frontiers in memory research.

As the population ages, understanding memory is vital for battling Alzheimer’s disease and other age-related dementias. But it’s not just the elderly who can benefit from memory research.

Only by understanding how memory works can researchers open the door to new treatments for psychiatric illnesses and learning disabilities.

“Memory is the most significant of all the mental processes,” Kandel said. “Memory is involved in every aspect of our lives.”