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Electrical Deep-Brain Stimulation Enhances Memory in Small Study

An electrical current sent deep into the brain improves memory, according to a study that suggests a novel approach to treating Alzheimer’s disease and dementia.

Seven volunteers with epilepsy who had electrodes implanted in their brains to detect the source of their seizures participated in the research to see if deep-brain stimulation improved their recall. The results published in the New England Journal of Medicine showed that information they learned while the stimulation occurred was easier to remember and use.

The volunteers had varying memory strength at the start of the study and all improved with the deep-brain stimulation, said Itzhak Fried, the lead researcher and professor of neurosurgery at the University of California, Los Angeles. The findings suggest a novel approach to improving memory and mental function in people with Alzheimer’s disease, dementia and trouble remembering as they age, he said in a telephone interview.

“Alzheimer’s disease is the big target here because it’s such a huge problem with people getting older,” said Matt Stead, a neurologist at the Mayo Clinic in Rochester, Minnesota, who wasn’t involved in the study. “This is probably one of the most hopeful things I’ve seen regarding Alzheimer’s disease in a long time, because none of the medicines seem to do much.”

Medtronic Inc., based in Minneapolis, sells a deep-brain stimulation device for Parkinson’s disease and obsessive-compulsive disorder, and is studying it for depression. St. Jude Medical Inc., based in St. Paul, Minnesota, sells a similar device in Europe and is conducting U.S. studies. Trying the technique to improve memory is a natural extension, said Andres Lozano, chairman of neurosurgery at the University of Toronto, who wasn’t involved in the research and is doing similar work.

‘Next Frontier’

“Ninety thousand patients have received deep-brain stimulation in the world, and about 10,000 patients get it every year,” Lozano said. “The next frontier is to consider placing electrodes in areas that control memory and cognitive function to see if it can help with disturbances in those areas.”

The volunteers in the study released yesterday played a video game where they acted as a taxi cab driver shuttling passengers across a virtual city. The electrodes received electrical stimulation while they learned to get to three stores, and were turned off for another three.

In a subsequent test, they were able to take shortcuts and get more quickly to the stores they visited while the stimulation was active. That showed improved spatial memory, a key component of everyday living such as finding your car in a parking lot and remembering where you stashed the keys, Fried said.

Brain Areas

The location of the electrodes was key, Fried said. Stimulation of the hippocampus, a key component of the brain that converts short-term experience into long-term memory, didn’t help. The hippocampus is one of the first areas where destruction from Alzheimer’s disease occurs. However, the stimulation was beneficial when it occurred at the entorhinal cortex, which leads to the hippocampus, an area getting increasing attention from Alzheimer’s disease researchers.

Tiny electrodes, measuring less than 2 millimeters in size, were placed a little less than 2 inches into the brain. None of the patients felt the stimulation.

“What we found here was a particular golden gate, a small area in the entorhinal cortex, where stimulation has a striking effect on memory,” Fried said. “This is an area of the brain which is critical in transformation of experience into lasting memories. Everything you perceive now, everything that’s committed to conscious memory, has to be funneled through this system.”

The U.S. National Institutes of Health and the Dana Foundation funded the research. The investigators used standalone electrodes in the study, rather than deep-brain stimulation devices from Medtronic or St. Jude.

Probing the Brain

The study shows it’s possible to reach circuits in the brain involved with processing memory and that electrical stimulation can enhance their function, Lozano said.

The new findings support his earlier work involving six Alzheimer’s disease patients who received constant deep-brain stimulation for a year. Half of the patients progressed more slowly than expected and one had a lasting benefit. Larger studies are now being planned. The approach also restored some of the brain’s ability to use glucose, suggesting it reactivated areas of the brain that were previously shut down, he said.

“This is the second study that shows you can stimulate somewhere along the memory circuit of the brain and get a benefit,” Lozano said in a telephone interview.

Theta Rhythm

The researchers believe the benefit stemmed from resetting the brain’s theta rhythm, altering the way large groups of cells involved in memory function work. The two studies stimulated different areas in the same segment of the brain, which Lozano compared to a subway car stopping at different stations.

Stead, who typically performs deep-brain stimulation to treat Parkinson’s disease, said the results mesh with earlier studies that show such stimulation can cause new neurons to grow and function normally. One man treated with brain stimulation for extreme obesity spontaneously recalled events from decades earlier, Stead said.

While it can take people about a year to get over the idea of having electrodes implanted in the brain, they typically don’t cause problems and the procedure can be done during a one-day hospital stay, he said.

“In the scope of brain surgery, it’s pretty minimal,” he said, comparing it to getting a pacemaker for the heart.

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