Study Explores Electrical Stimulation as an Aid to Memory

Scientists have for the first time improved memory by applying direct electrical stimulation to a key area in the brain as it learns its way around a new environment.

The stimulation, delivered through electrodes inserted into the brains of epilepsy patients being prepared for surgery, sharply improved performance on a virtual driving game that tests spatial memory, the neural mapping ability that allows people to navigate a new city without a GPS.

Experts said that the new study, appearing Thursday in The New England Journal of Medicine, was tantalizing but not yet conclusive, because the number of patients tested — six — was small, and the biological effects of electrical stimulation are still poorly understood. But it comes at a time of growing excitement in the study of memory and its disorders; only last week, researchers reported strong evidence that damage associated with Alzheimer’s disease spreads through the brain — beginning in the same area targeted in the new study.

“People should run to replicate this study, because the implications are incredibly exciting, both for understanding the mechanism for encoding new memories, and ultimately for the treatment of neurological diseases” like dementias, said Michael J. Kahana, a neuroscientist at the University of Pennsylvania, who was not involved in the research.

Scientists have enhanced learning with electrical stimulation before, many times in rodents and at least once in a human, as a side-effect of stimulation for another purpose. In the 1980s, researchers directly stimulated a brain region in humans called the hippocampus, which is critical in memory formation; but the current interfered with new memories.

In the new study, a team of doctors at the University of California, Los Angeles, focused on a neighboring area, called the entorhinal cortex. The entorhinal cortex is now the center of intense study. It is where the first signs of damage in Alzheimer’s disease usually appear, and it has dense connections to the hippocampus, through which it transmits the streaming data of daily experience, studies suggest — presumably for sifting and encoding.

The researchers threaded electrodes into the brains of seven people with severe epilepsy, a standard procedure allowing surgeons to pinpoint the squalls of brain activity that cause seizures, before operating.

The patients worked to master a taxi-driver game, in which the goal is to quickly drop off passengers at various locations in an unfamiliar virtual city. They “drove” to six places, and during three of the trips an electrode in their entorhinal cortex ran a low current — enough to stimulate neurons in the area but not enough to interfere with function or tip off the patients.

Sure enough, on a test given later, each patient did far better in returning to the three “stimulated” destinations than to the other three, which were equally difficult to find. The improvement ranged from 40 percent to nearly 90 percent, as measured by the length of the path that the patients used.

The stimulation also increased so-called theta waves in the hippocampus, a low-frequency global rhythm that seems to coordinate the firing of neurons and aid memory.

“The bottom line is that, you turn this thing on, and later on you remember better what you learned,” said Dr. Itzhak Fried, the senior author and a professor of neurosurgery at U.C.L.A. and Tel Aviv University. His co-authors were Nanthia Suthana, Dr. Zulfi Haneef, Dr. John Stern, Roy Mukamel, Eric Behnke and Barbara Knowlton, all of U.C.L.A.

Previous studies have identified neurons in the entorhinal cortex called grid cells that are involved in spatial navigation, but it is not yet clear how spatial memories are formed or which cells are most critical. The famous amnesic patient known as H.M., who had much of his hippocampi (there are two, one in each hemisphere of the brain) and neighboring entorhinal tissue surgically removed to control seizures, learned to draw a floor plan of the house he moved into after his operation.

“Given these anatomical uncertainties, it may be premature to draw firm conclusions about the locus of memory enhancing stimulation,” Suzanne Corkin, a neuroscientist at the Massachusetts Institute of Technology and author of a coming book about H.M., “Permanent Present Tense,” said in an e-mail.

Still, the potential upside to developing a way to juice the memory circuits is enormous. People with severe dementias, in addition to their loss of identity, often cannot navigate their way to the corner store, or even the bathroom — a humiliation that even a crude electronic aid might help resolve. Tens of thousands of people with Parkinson’s disease and other disorders benefit from implants that stimulate tissue deep in the brain.

“The potential application of deep-brain stimulation in amnesic disorders is enticing,” wrote Sandra E. Black of the University of Toronto, in an editorial accompanying the study. The next step, Dr. Black wrote, is “finding the best structure for stimulation and the best way to evaluate its effects.”