Studying Oversize Brain Cells for Links to Exceptional Memory

In 2010, a graduate student named Tamar Gefen got to know a remarkable group of older people.

They had volunteered for a study of memory at the Feinberg School of Medicine at Northwestern University. Although they were all over age 80, Ms. Gefen and her colleagues found that they scored as well on memory tests as people in their 50s. Some complained that they remembered too much.

She and her colleagues referred to them as SuperAgers. Many were also friends. “A couple tried to set me up with their grandsons,” Ms. Gefen said.

She was impressed by their resilience and humor: “It takes wisdom to a whole new level.”

Recently, Ms. Gefen’s research has taken a sharp turn. At the outset of the study, the volunteers agreed to donate their brains for medical research. Some of them have died, and it has been Ms. Gefen’s job to look for anatomical clues to their extraordinary minds.

“I had this enormous privilege I can’t even begin to describe,” she said. “I knew them and tested them in life and in death. At the end, I was the one looking at them through a microscope.”

Ms. Gefen and her colleagues are now starting to publish the results of these post-mortem studies. Last month in The Journal of Neuroscience, the scientists reported that one of the biggest differences involves peculiar, oversize brain cells known as von Economo neurons. SuperAgers have almost five times as many of them as other people.

Learning what makes these brains special could help point researchers to treatments for Alzheimer’s disease and other kinds of mental decline. But it is hard to say how an abundance of von Economo neurons actually helps the brain.

“We don’t know what they’re doing yet,” said Dr. Mary Ann Raghanti, an anthropologist at Kent State University who was not involved in the new study.

As soon as the Northwestern scientists began enrolling SuperAgers in their study in 2007, the team took high-resolution scans of their brains. The SuperAgers had an unusually thick band of neurons in a structure called the anterior cingulate cortex, the scientists found; it was 6 percent thicker on average than those of people in their 50s.

After some of the SuperAgers died, the Northwestern scientists looked more closely at these structures. The researchers stained the tissue, put it under a microscope and were struck by an obvious abundance of von Economo neurons. “It really jumped out,” Ms. Gefen said.

The Ukrainian anatomist Vladimir Betz first noticed these giant “spindle shaped cells,” as he called them, in 1881. In the 1920s, the Austrian anatomist Constantin von Economo carried out the first detailed study of the cells, but his research sank into obscurity. It wasn’t until the 1990s that researchers rediscovered the stick-shaped neurons, calling them von Economo neurons in 2005.

These neurons grow only in a couple of regions of the human brain, including the anterior cingulate cortex, and they can be four times bigger than other brain cells. Instead of a typically cone- or star-shaped body, von Economo neurons are long and thin, with branches that extend far across the brain.

Scientists have found von Economo neurons in only a few other mammals, such as apes, whales and cows. It’s possible that they emerged repeatedly when different mammals faced the same evolutionary challenges. But it’s not clear what challenges such diverse species might have in common.

Clues to the purpose of the neurons have come from researchers studying brain disorders. People who suffer from a form of senility called frontotemporal dementia lose many of their von Economo neurons. Alcoholics have 60 percent fewer von Economo neurons than average in one region of the brain called the frontal insula.

John M. Allman of Caltech, who has studied von Economo neurons for 20 years, suspects that the neurons provide long-distance transmission of nerve impulses. The large size of the cells helps maintain electrical signals as they travel across the brain.

“My guess is they represent a fast relay,” he said.

Certain kinds of thought may create a special demand for speed in large brains. By transmitting signals from the anterior cingulate cortex and frontal insula to other regions of the brain, said Dr. Allman, von Economo neurons may help us manage impulses and stay focused on long-term goals.

The possibility that these neurons also may keep old minds sharp is intriguing, Dr. Allman said, although he noted that the new results were based on a small number of subjects. Ms. Gefen and her colleagues examined the brains of five SuperAgers, comparing them with five average people in their 80s and five others with mild memory impairments.

Extra von Economo neurons might make the brain more resilient. But no one can say how some people end up with such an abundant supply of the cells. Did they start out with a lot of these neurons, or somehow manage to preserve them over the years?

Ideally, Ms. Gefen said, she would like to study people for many decades to see how their von Economo neurons develop and endure.

“But who wants to wait 65 years?” she added. “My mother would kill me, because she wants the Alzheimer’s cure now.”