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Randy Buckner wants to know what makes us remember

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AAAS Fellow Randy Buckner's research is driven by his desire to understand what makes the human brain exceptional and how brain activity gives rise to complex human behaviors. (Photo: Courtesy of Randy Buckner)

His name was Henry Molaison, better known in scientific circles as patient "H.M." Molaison suffered from epilepsy and in the 1950s underwent an experimental surgery to correct his condition. The surgery gave him some relief from his seizures but left him without the ability to form new long-term memories.

"His was such an extraordinary case because it tells us that specific parts of the brain are critical for memory," says AAAS Fellow Randy Buckner. "It was fascinating to learn that the damage caused by removing certain parts of the brain could be so selective, as many of his other abilities and faculties were untouched by the surgery."

Buckner remembers specifically the first time he heard the story of patient H.M. It was in a neuropsychology class at Washington University in St. Louis when Buckner was an undergraduate. It would serve as the catalyst for his life's work.

Buckner is a professor of psychology and of neuroscience at Harvard University. Much of his research is driven by his desire to understand what makes the human brain exceptional and how brain activity gives rise to complex human behaviors, such as planning out our long-term futures and rehashing the subtleties in our social interactions. This means he's especially drawn to the association networks of the brain—higher-level networks that are responsible for thinking and many other functions that are well developed in humans. "It's a puzzle to understand how in a relatively short period of evolutionary time the remarkable capabilities of the human brain could evolve," Buckner says.

One of these extraordinary capabilities: how we use our memory to plan for the far-off future or imagine how past events could have happened differently. Buckner studies episodic memory, the ability to remember what happened when and with whom. Buckner wonders why this type of memory is so highly developed in humans. "Humans are highly social animals," he says, \and I started to wonder if some of our memory and emotional systems have evolved to contribute to our ability to solve complex social situations."

To answer these questions, Buckner and his colleagues use neuroimaging techniques, like functional magnetic resonance imaging (fMRI), to measure activity in brain networks. He looks for how individual differences in those networks are related to how people differ and how they respond in different situations as well as how those networks break down, for example in Alzheimer's disease.

During the course of one such fMRI experiment, Buckner and his colleagues stumbled upon an unexpected discovery. As a control condition, they asked participants in the fMRI scanner to just lay there and do nothing while their brains were scanned. Buckner found that a specific network of brain regions was more active during this passive control task than during the active tasks they were studying. "We call it the default network," Buckner explains, "because people default to using the network when left to their own devices."

With more study, Buckner and his colleagues learned that the default network is also active when you ask people to remember what they did yesterday or think about what they're going to do in the future. "If you let your mind wander, there's a good chance you will think about what you did yesterday or imagine something you might do later," he says. Buckner calls this ability "self-projection" and noted that "humans do it much of the time.\" The default network is used by people to imagine themselves in different scenarios, and this is one kind of ability that may be intimately linked to what makes humans so extraordinary. "We're mental explorers, we can imagine different alternatives and then make a choice," Buckner says.

The default network relies heavily on the brain's association regions, areas devoted to higher-level cognition and information processing, which are expanded in the human brain as compared with other animals. "We know that humans spend a great deal of time imagining and thinking about different alternatives using their memory," Buckner says. He believes this well-developed human ability is adaptive. It prepares us for the future. "In humans, our memory allows us to imagine what might happen next and come up with multiple different scenarios. We can also analyze things that happened to us in the past and try to learn from them. We can use these abilities to avoid future bad situations without actually doing them, without depending on trial-and-error learning."

Understanding the default network is interesting in terms of understanding what makes humans unique, but it turns out to also have a critical role in some brain disorders. Higher-order networks involved in thinking and imagining are disturbed in several mental illnesses and the default network in particular is targeted early in the course of Alzheimer's disease. Part of Buckner's research is focusing on learning what makes these brain networks vulnerable and devising methods to measure their function, which can then be used to develop treatments.

"Like so many families, I've had relatives who have had Alzheimer's disease," Buckner says. This personal connection has affected the direction of his research. Buckner studied normal memory in his early career, but personal interest drove him to start asking research questions about how memory breaks down in Alzheimer's disease. "It's helped to focus my work," Buckner says. "I know I'm studying important questions because I've seen these deficits in the patients I interact with and also members of my own family."

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AAAS Fellow Randy Buckner's research is driven by his desire to understand what makes the human brain exceptional and how brain activity gives rise to complex human behaviors. (Photo: Courtesy of Randy Buckner)
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Mary Bates, Ph.D.