In an experiment likely to raise new hopes for those with memory-robbing diseases such as Alzheimer's, researchers have found that sending an electrical jolt to a part of the brain that plays a key role in memory improved people's ability to learn -- and remember -- their way across an unfamiliar landscape.
The study, conducted at UCLA and published in Thursday's edition of the New England Journal of Medicine, was small and highly preliminary, involving just seven patients with epilepsy. But deep brain stimulation helped all seven subjects -- including some who suffered memory impairment-- navigate faster and more accurately through a virtual town.
Since the treatment also gave a boost to subjects with no signs of dementia, the study is likely to reignite a simmering debate over the ethics of enhancing the mental capacities of people in perfect cognitive health, experts said.
The new results build on animal studies that found deep brain stimulation not only boosted activity in the brain's memory centers, but spurred the growth of new brain cells when those regions were damaged. The fact that the same technique improved memory performance in humans makes some researchers optimistic that it might be a way to block or reverse the destruction of brain cells in patients with Alzheimer's.
Though physicians are now able to diagnosis Alzheimer's disease earlier than ever -- sometimes years before memory lapses and other cognitive changes become evident -- they are still at a loss to alter the disease's progress.
Deep brain stimulation involves the insertion of guide wires through the skull and into the brain, where they deliver electrical current to clusters of neurons that no longer function properly. It is widely used in the treatment of Parkinson's disease, in which damage to regions of the brain's motor cortex cause tremors, rigidity and unsteady gait. About 90,000 Americans have had the battery-powered, stopwatch-sized devices implanted in their brains, and they often show marked improvement. But the neurostimulator has not been found to slow or block the progression of that disease.
The technique is also being used for patients with epilepsy, to disrupt the storm of electrical current in the brain that causes seizures. The patients who took part in the memory trial were candidates for this treatment, and in preparation for surgery they had electrical probes inserted in their brains -- giving researchers the opportunity to conduct their experiment.
The goal was to explore whether stimulation to two key memory regions of the brain would deliver improvement in cognition. With their heads immobilized, the patients had electrodes placed in their brains. Then they played a virtual game of taxi driver, learning their way through an imaginary town in order to reach six destinations.
While navigating the new landscape, the subjects sometimes got deep brain stimulation to one of two areas -- the hippocampus or an adjacent structure called the entorhinal cortex -- and other times got no neurostimulation at all.
The researchers found that when subjects' entorhinal region was stimulated while they navigated through the maze for the first time, they were speedier and more accurate in learning the way to certain destinations than when they explored a similar maze without stimulation.
For instance, subjects outlined routes to stores that were 64% shorter, on average, when the entorhinal cortex was stimulated compared with when it was not. When electrodes delivered stimulation directly to the hippocampus, some subjects improved their performance while others got worse.
Itzhak Fried, a UCLA neurosurgeon who worked on the study, called the hippocampus "the master organ of memory." But he said the greater improvements seen in the memories of patients who got stimulation to the adjacent entorhinal region suggested a new target for treating memory loss.
"The entorhinal cortex is a gateway into the hippocampus," Fried said. "If you are to consciously recollect incoming information, it needs to be processed here."
In an editorial accompanying the study, University of Toronto neurologist Sandra E. Black called the potential application of deep brain stimulation in the treatment of memory disorders "enticing."
And Dr. Maria Carrillo, scientific director of the Alzheimer's Assn., agreed that electrically stimulating the brain's memory centers may hold greater promise. But she cautioned that the complexity and breadth of destruction in Alzheimer's make it resistant to simple fixes.
"It's a little early to talk about deep brain stimulation as a treatment for Alzheimer's disease," she said. "But certainly it's tantalizing."
The study has many drawbacks beyond its small size, including the fact that participants did not have a uniform level of memory impairment and that the tests measured only spatial memory, not memory of faces, places and words, the researchers said.
Andres M. Lozano, a neurosurgeon at the University of Toronto who has conducted similar experiments in mice, said this line of research already had piqued the interest of people with normal memory function who seek a little intellectual edge.
"These are major ethical issues society will have to grapple with when the time comes," Lozano said.
"This opens up a Pandora's box."