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A new study suggests that driving electricity deep into the brain can boost memory, shedding light on a mysterious neurological process and opening the door for Alzheimer's disease treatments.
Researchers from the University of California at Los Angeles used needle-like electrodes to send pulses of electricity into the brain's memory system buried more than an inch inside the temporal lobes of seven epilepsy patients. The technique -- called deep brain stimulation -- acts like a pacemaker, tweaking brain activity with tiny, rhythmic shocks.
"The hippocampus and entorhinal cortex in the medial temporal lobe, these structures are critical sites for transforming experiences into memories," said Dr. Itzhak Fried, a UCLA neurosurgeon and lead author of the study published today in the New England Journal of Medicine. "When we applied stimulation not in the hippocampus but in another structure that leads to the hippocampus, we saw an improvement in memory performance."
Fried and colleagues used a virtual city to test recollection of routes and destinations before and after deep brain stimulation. The patients played the role of taxi drivers shuttling people around town. And when they learned the directions during deep brain stimulation, they remembered them better.
"The path to the target was shorter, and patients got there quicker," said Fried.
The patients volunteered for the memory study after having electrodes implanted to determine where their seizures were starting. Some of them had memory deficits related to their epilepsy, but all of them showed improvement with stimulation, Fried said.
Deep brain stimulation has been found to tame tremors in Parkinson's disease, calm compulsions in obsessive compulsive disorder and even ease appetite in obesity. But what exactly it does inside the brain remains somewhat of a mystery.
"It's fair to say there are a lot of unknowns about how deep brain stimulation works," said Fried.
In Fried's study, the stimulation seemed to reset the rhythm of nerve firing between the entorhinal cortex and the hippocampus -- a rhythm that's "critically important" for memory, Fried said.
"Maybe this type of resetting has a beneficial effect on memory," said Fried. "It may be influencing the way groups of neurons cooperate and work together."
A previous study found, somewhat serendipitously, that deep brain stimulation enhanced memory in a patient being treated for obesity. And a small trial in six people with mild Alzheimer's disease suggested that deep brain stimulation may even slow cognitive decline.
"There's a lot of interest in this type of approach," said Fried. "But obviously, it will require very careful, rigorous studies to see whether deep brain stimulation can be applied to patients with memory impairments, such as Alzheimer's disease, where indeed one of the first signs is impairment of memory and function in the area of the brain where we applied the stimulation in our study."
In Alzheimer's disease, an accumulation of abnormal protein plaques and tangles gradually destroy the brain's memory center. Dr. Sandra Black, a neurologist at the University of Toronto's Sunnybrook Health Sciences Center and author of an editorial published in the same journal as the study, said the prospect of using deep brain stimulation to boost memory in people with brain damage or disease is not "science fiction."
"If we get to a point where we can control [Alzheimer's disease] with some of the new drugs in development and stabilize it by counteracting amyloid [plaques] or tau [tangles], then this might be an important way to help that area of the brain recover," she said.
Studies in animals suggest deep brain stimulation may even spur new nerve growth. But, said Black, "you'd have to catch people at a time when there was still some capacity to regenerate," meaning very early in the Alzheimer's disease progression.
Dr. Jeffrey Noebels, a professor of neurology at Baylor College of Medicine, said the idea that memory storage and retrieval could be electronically enhanced "is fascinating." But "just as in drug testing, extreme care must be exercised to avoid unleashing undesirable and lasting effects arising from the very plasticity and rewiring of the brain that is likely to arise," he said.
Noebels said stimulating the brain's memory center could trigger a seizure, spawning a "downward, toxic spiral of neural hyperactivity, axon rewiring and cell death in the very circuits we would like to preserve."
"My fear is, in early stages of Alzheimer's, continuous stimulation of the entorhinal cortex could actually be too much too soon," he said.
Fried agreed that caution is critical in considering deep brain stimulation as a treatment for people with memory loss from brain damage or disease, but said the possibility signaled "a new era" in medicine.
"Creating this type of interface with areas of the brain may be used to really augment impaired function in neurological patients," he said.
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