Mysteries of Memory

Think about yesterday's lunch and a variety of details may leap to mind, each of them employing a different section of your brain. The olfactory system calls up what the meal smelled like, while the visual cortex retrieves images of the restaurant you ate in and the temporal lobe recalls the sound of your waitress's voice. Scientists have long suspected that every recollection—from the mundane to the momentous—ignites a distinct pattern of neurons. But for decades, they have struggled to understand how the brain assembles such disparate elements into a single coherent memory, one that can be retrieved intact, spontaneously or on demand, hours, days or even years after the fact. "It's not like a tape recorder where you store it all on one cassette," says Lynn Nadel, a neuroscientist at the University of Arizona in Tucson. "There's more than one PLAY button to hit."

It's no trivial matter. One of the most devastating effects of dementia and Alzheimer's disease (expected to afflict 14 million Americans by 2040) is the loss of what's known as episodic memory—the capacity to remember experiences in detail. Despite years of research and some initial progress, the ability to restore this function to aging or diseased brains continues to elude doctors. But research published earlier this month in the journal Science has provided some important clues into how the brain builds memories.

UCLA neuroscientist Itzhak Fried and his Israeli colleagues measured neural activity in the brains of 13 study participants as they watched short video clips of shows like "Seinfeld" and "The Simpsons." Afterward, while their brains were still being monitored, subjects were asked to describe whichever of the video clips came to mind. The same neurons that had fired as they watched a given clip fired again when they recalled that clip. In fact, researchers were able to predict which clip a subject was about to remember, as corresponding neurons flared up seconds ahead of actual remembering.

The findings offer the first proof of a long-held assumption—that reactivation of the neurons initially involved in an experience forms the basis of human memory. "Being able to see human memory recall in action, in real time, is unprecedented," says MIT neuroscientist Matthew Wilson. "We've suspected for quite a while that storage and retrieval would be concentrated in the same cells, but never had the proof until now."

As exciting as that finding may be, however, some memory experts say the true significance of Fried's study lies not in when the neurons fired, but in where they were located—the hippocampus. One of the earliest and most common signs of Alzheimer's disease is that patients start getting lost in places familiar to them. The hippocampus, a thin slice of tissue tucked deep in the brain, is known to play a role in the ability to remember and navigate through a given place, a process known as spatial learning (it has also been implicated in long-term memories, which this study did not examine). The involvement of these same cells in the storage and retrieval of memories suggests that location may be the key to human recollections, the defining element that summons all the other elements together to reconstruct an event.

"We have been searching for a long time for the scaffolding upon which human memories are created and stored," says Nadel. "These findings show us that the physical space in which events occur may, in fact, be that scaffolding." In Alzheimer's and dementia patients, he says, this scaffolding breaks down somehow. And from the inability to find their way home from the neighbor's house, Alzheimer's and dementia patients soon lose the capacity to remember their loved ones' faces.

The power of physical place to ignite a memory has guided addiction research for years. Therapists have long counseled recovering addicts to avoid the places associated with their substance abuse, lest they trigger a relapse. But its potential role in Alzheimer's and dementia treatments remains less clear. "This certainly points us toward cognitive therapies," says Wilson. "But it's hard to get more prescriptive; when it comes to human memory, we are still just uncovering the basics."

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